8/12/2019 1-s2.0-002432057590017X-main

1/14

Li te 8ai enoe~ Vol 16, PP 187- 200 Pergamon PreeePr i nt ed i s t he D S ~

M NI RBVLSi P

WiATDOES I ADI VI DUALHO~ G MEAR TO A M USEY

Paul Brai n

Depar t ment of Zool ogy, Uni vers i ty Col l ege of Swansea, SA2 PPSouth Wal es, U

Summary

Some r ecent st udi es r el at i ng the ef f ects of i ndi vi dual housi ng i sol ati on) and group housi ng to behavi or physi ol ogy and neuro-chemstry i n l aboratory rats and m ce are revi ewed and t heae~account erel ated to compar abl e i nf or mat i on deri ved f rom ezper i ment s empl oyi ng soci al stresses e g subj ecti ng the eai mal to def eat The data i sdi scussed i n rel at i on t o the probl em of whether i ndi vi dual housi ngconst i t ut es a st ress i n term of adr enocor t i cal and adrenalmedul l ary r i mcti oni ng) i n these speci es, as i t appears to do i npri mat es I n spi te of the l arge number of papers whi ch ascri be thebehavi oral and endocri ne changes obtai ned i n i sol at i on versusgr oupi ng compari sons t o t he ef f ects of t he i sol at i on- i nduced stresssyndr ome , i t i e concl uded that i n term of adrenal f uncti on, therei s l i t t l e evi dence that i sol at i on gar ae const i t ut es a stress i n ratesad mce sl t hough there i s some evi dence that adr enocor t i calreact i vi ty i s i ncreased by housi ng eai mal s i n t hi s manner I t shoul dbe noted t hat the w l d progeni tor of the l aboratory str ai ns of housemouse of ten appears t o evi dence t er r i t or i al i t y The vi ew i s adveacedthat the i sol ated condi t i on i n mal e mce may resul t i s changes char a-ct er i st i c of terri tori al dom nance . Thi s may represent a mechani smf or i nduci ng soci al or terr i tor i al stabi l i ty i n t hi s speci es I tappears that ezper i ment s i nw vi ng physi cal i sol ati on i n l aboratoryi ndent s are unl i kel y to provi de good model s f or the ef f ects of soci al depr i vat i on i n man I t i s thought that mor e st udi es empl oy-i ng measurement of hormone t i t er s i n bi ol ogi cal sampl es obtai ned asa r esul t of non- str essf ul pxrocedur es, w l l l ead t o a cl earer underateadi ng of the eff ects seen i n i sol at i on versus groupi ng studi es Or gan wei ght studi es of ten appear to be very msl eadi ng part i cul arl ryi n f emal e rodents I t i e al so hoped t hat other studi es w l l concexat hemsel ves wth eff ect s of i sol at i on w th respect t o other soci alcues i n rodents i ncl udi ng odors and ul t rasound

~Thi e work has been supported by grants f romThe Medi cal ResearchCounci l and the Royal Soci ety I woul d l i k e to than Dr Davi dBentoa, Dr Cather i ne W l son, Char l es i hrana end Angel a Pool e f or~ei uabl e di scussi on sad advi ce

187

8/12/2019 1-s2.0-002432057590017X-main

2/14

18 8 Contactual i sol at i on and Mca Vol l b, No 2

D f f erenti al Houei ~ end Aggressi veness

Al though rodent soci al behavi ors necessari l y depend on a vari ety ofsensory modal i t i es, mer e physi cal i sol ati on the maj or f ormof i sol ati onstudi ed) has been shown to have many prof ound behavi oral and physi ol ogi calconsequences i n l aboratory str ai ns of house mce Mus muscul us L . Forexampl e, aggressi veness of the mal e mouse i s i ncreased by such i sol ati onAggressi veness, as used here, ref ers to the type of mot i vat i on whi ch tends toresul t i n a hi gher i nci dence and i ntensi ty of overt i ntr aspeci f i c f i ghti ng i na neutral arena I t shoul d be noted that such di verse behavi ors as mouseki l l i ng i n rats, i ntermal e f i ghti ng i n mce, shock el i ci ted aggressi on i nei ther mce or rats and attacki ng a penci l al l of whi ch have been used asi ndi cators of aggressi veness ) , are unl i kel y to have the same i nternal orsi tuati onal determnants 1 Physi cal i sol ati on seem to have i t s mostpotent acti on oa i ntermal e f i ghti ng behavi or i n mce 2, 3, 4, 5, 6, 7, 8, 9, 10, 11,12 The ef f ects of i sol ati on on thi s behavi or have been shown to be progressi ve 9, 13, 14) A si ml ar acti on on f i ghti ng behavi or has been shown i sother rodent speci es e . g the gerbi l 15 , the hamt er 16 and the rat 1 1819, 20) Certai n workers have i ndi cated the i mportance of pri or experi enceto agoni sti c encounters i n rodents 13, 21, 22) and some reports have suggest edthat earl y soci al i sol ati on cea reduce f i ghti ng behavi or i n mce 23,24) Conversel y, i sol ati ng mal e gui nea pi gs soon af ter weani ng has been shown toi nduce more aggressi veness than i sol ati on i n adul thood 25 However , i tappeara, i n general , that i sol ati on does cause as augmentati on of f i ghti ngbehavi or i n the mouse and other speci es

D f f erenti al HOU91I I g and Adrenocorti cal Functi oni ng

Al though the reported resul ts and i nterpretat i ons are of ten at vari ance,there i s al so much evi dence that adrenocorti cal acti vi ti es di f fer i n i sol ated

sad group- housed mal e end f emal e mce 10, 11, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36,37, 38, 39) Si ml ar resul ts have been descri bed i n other speci es 40, 41, 42, 43)

So f ar ae the mouse i s concerned, there has been support f or the vi ewthat physi cal i sol ati on consti tutes a hi gh stress condi t i on e g 8 sad,al so, that such housi ng consti tutes a l ow stress condi t i on e . g 39

Measures of adrenocorti cal acti vi ty have been very di f f erent i n di versestudi es, rangi ng f rom rel ati ve adrenal wei ght, through l eucocyte count andadrenal ascorbi c aci d l evel s, to the di rect determnat i on of ci rcul ati ngl evel s of adrenocorti cal hormones Even di rect measurement of hormone ti termay be i mperf ect as such determnati ons rarel y take account of ci rcadi anvari at i ons i s adrenocorti cal acti vi ty, proporti ons of bound and f ree hormone,di str i but i on i n di f f erent physi ol ogi cal compartments etc Bi ochemcal methods

have al so been appl i ed to bl ood sad t i ssue sampl es obtai ned by di f f erentmethods whi ch di f f er i n t hei r str easf ul ness e . g bl ood sampl i ng may be bydecapi tat i on or af ter anaest hesi a and/or restr ai nt

Vari abl es, such as those reported above, coul d i nf l uence the resul ts oPcompari sons between i sol ated and group- housed mce Al though there i s a comprehensi ve seri es of papers on i sol ati on stress i n mal e 8 and f emal e mce 34 , 35, 48, 49, 50 as wel l as a si ml ar body of evi dence i n the rat 51, 52, 53) ,i t woul d appear that there i s a concenaus, as a resul t of the maj ori ty ofstudi es i n whi ch hormones are measured, i n f avour of the vi ew that i sol ati on

se i s l ess stressf ul than group housi ng However , i sol ated mce appearto show a greater response to addi t i onal stresses, f or exampl e, i sol ated mceare hypersensi ti ve to di f f erent types of envi ronmental sti mul i i ncl udi ng handl i ng 54 noi se 55,56) el ectroshock 57), restr ai nt 58 or 15 w nsattack by a t rai ned f i ghter 59 Hatch et al 52 have al so shown that the

8/12/2019 1-s2.0-002432057590017X-main

3/14

8/12/2019 1-s2.0-002432057590017X-main

4/14

19 Contactual I sol ati on and Mce Vol 16, No 2

compl i cated by di f f erences i n i nterpretat i on, methodol ogy etc but a f ewf i ndi ngs of general appl i cat i on may be i ndi cated

I sol ati on i n the mal e mouse has been reported to resul t , f or exampl e, i ndecreased l evel s of neural N- acetyl - L- aspart i c aci d ( 71) , as wel l as changesi n many other neurochemcal s 14 , i ncl udi ng vari abl e ef f ects pa brai nserotoni n 5HT l evel s (5, 6, 69, 72 . 73 The moat consi st ent f i ndi ng concerni ngputat i ve neurotransmt ters i n the brai n appears to be that i n i sol ated mcethe turnover rate for 5HT and NE i s l ower than that f ound i n group- housed mce Thi s has been i ndi cated by the presence of l ower l evel s of 5- hydroxyi ndQ eacet i caci d the chi ef degradati on product of 5HT and NE i n the brai n of mce i sol a-ted for at l east 14 weeks 58 I n addi t i on, i n i ndi vi dual l y housed mce therei s a rel ati ve decrease i n the rate of accumul ati on of both amnes af ter treat-ment w th monoamne oxi dase i nhi bi tors ( t ranyl cypromne or pargyl i ne) (5, 6, 14,68,73) when contrasted w th group- housed mce

Not al l report s agree w th these general f i ndi ngs Some suggest thatthere are no di f f erences i n the monoamne acti vi ti es of i sol ated or groupedmce ( 3, 35 . 75 Wel ch and Wel ch 74 even f ound that norepi nephri ne l evel swere hi gher i n acutel y i sol ated mce, a resul t whi ch was probabl y due to thestressful ef f ects of a sudden change of condi t i ons

Changes i n both 5HT and NE may be rel ated to the earl i er report ed i so-l at i onal ef f ects on aggressi veness, as Wel ch and Wel ch 14 have concl uded,that the tendency to f i ght i s di mni shed by i mpai ri ng the bi osynthesi s ofneural catechol amnes and serotoni n I t i s al so been recent l y reported thatneural changes i n 5HT may exert prof ound i nf l uences on the f uncti oni ng of therodent pi tui tary- adrenocorti cel aai s ( 143) , i adi cati ng a rel ati onshi p betweenthese changes i s putati ve neurotransmtter concentrat i ons and the producti on ofgl ucocorti coi ds

D f f erenti al Housi ng and Drug Sensi ti vi ty

Grouped mce are more sensi t i ve to ef fects of d-amphet amne than i sol atedmce 76 Si ml ar resul ts have been reported concerni ng a vari ety ofsympathommet i c drugs by Greenbl att and Ost erberg 77 Hoxever, thi s al soappears t o be an acute ef f ect because when si ml ar experi ments on drug toxi ci tyare carri ed out on ani mal s whi ch have been i sol ated or grouped f or severalweeks rather than j ust di f f erenti al l y housed i mmedi atel y post treatment,amphetamne proves to be mor e toxi c to the pre-i sol ated ani mal s ( 3, 67, 78)whereas tranqui l i zers, such as reserpi ne and chl orpromazi ne, have been reportedto have greater acti ons on pre- grouped ani mal s (79, 80)

Def eat and B ochemcal Changes

As wel l as i sol ati on havi ng been shown to i nf l uence behavi or sadphysi ol ogy i n the mouse, a seri es of rel ated studi es have been report ed i nwhi ch the ef f ects of the st ress of defeat on such vari abl es have been descri bed Subj ecti ng mce to def eat i ncreases adrenocort i cal act i vi ty (13, 81, 82) ,as does groupi ng, an ef f ect whi ch may occur, gi ven a hi story of def eat , evenwhen physi cal attack i s precl uded 83 Def eat al so al ters whol e brai n,hypothal amc, eaygdal oi d and f rontal corti cal l evel s of the putati ve neuro-t ransmtt ers, such as serotoni n and nor- epi nephri ne (14, 84) Such ezposure hasal so been shown to al ter 5- Ydroxytryptophan decarbo~grl ase acti vi ty i n thef rontal cort ex and the amygdel e (85)~as wel l as changi ng l evel s of RNA bases i nvari ous regi ons of the brai n 86 The most str i ki ng f i ndi ng i n thi s l i mtedaeri es of studi es i s that serotoni n shows ea i ni ti al decl i ne i n t he hypothal a-mc and aa~gdal oi d areas of the brai n f ol l owed by an i ncrease af ter prol onged

subj ecti on to defeat , whereas l evel s of thi s putati ve neurotransmt ter show a

8/12/2019 1-s2.0-002432057590017X-main

5/14

vol 16, No Contactual I ool at i on and l ce 191

gradual decl i ne i n the f Yont al cor t i cal r egi on Changes i n r egi onal concent rati ons of nor epi nephri ne are gener al l y mrror i mages of changes i s ser ot oni nl evel s

Changes i n hypothal amc l evel s of l utei ni zi ng hor mone al so occur f ol l ow-i ng subj ecti on to def eat 87, 88) Prol onged aggr essi ve i nteract i on has beenahr nm to cause suppr essi on of the wei ghts of sex accessory gl ands 89) anddecl i nes i n the pr oduct i on of testi cul ar andr ogens 90) i s subor di nat e but notdomnant mce

Subj ecti ng mal e mce to def eat has al so been reported to el evate adrenalmedul l ary tyrosi ne hydr oryl ase and phenyl ethaaol amne N methyl t ransferaseact i vi ty 91) and pl asma l evel s of epi nephri ne and nor epi nephri ne 92) Wel ch sad Wel ch 14) have al so reported that the stress of def eat progressi vel yel evat es the l evel s of adrenal epi nephri ne sad norepi nephri ne Def eat al soappears t o i nf l uence pi t ui t ary- t hyroi dal act i vi ty i n the mouse 93) i ndi cat i ng

t hat t hi n gl and al so may f uncti on di f f erent l y i n i sol ated and grouped member sof t hi s speci es

Cor r el at i on of D f f e r ent i al ouai ag sad Def eat Experi ments

I n spi te of or perhaps because of , thi s pl ethora of bi ochemcal andbehavi oral i nf or mat i on, there s t i l l remai ns consi derabl e doubt about the exactrol e of i sol at i on i n the mouse The tr adi ti onal vi ew i e that i sol at i on i nr odent s, ae i n pri mates 96) consti t ut es a stress i n t er ms of soci aldepr i vat i on and that i t has i t s acti on oa behavi or sad endocri nol ogy byi ncreasi ng the i r r i t abi l i t y of these ani mal s Such a posi t i on i s f r equent l yt aken by Psychophar macol ogi st s e . g 9) and, i n addi t i on t o the studi es onf emal e mce i ndi cat i ng i sol at i on st r ess , there have been a number of reportswhi ch i ndi cate that earl y i sol at i on may l ead to def i ci enci es i n behavi or i nsome r odent s For exampl e, earl y i sol ati on has been report ed to cause part i ali mpai r ment of sexual behavi or i s mal e gui nea pi gs 97, 98) and mal e rata 99) Such t reatment has been shown to resul t i n a l owered brai n wei ght i n rata 100) However , i t shoul d be not ed that t he ef f ects of earl y i sol at i on are notnecessari l y rel ated t o the effects of such housi ng i n l at er l i f e I t coul dal so be t hat some of these det r i ment s i n sezuel behavi or are rel ated toi ncreased aggr essi veness

Al t hough there are many reported except i ons sad the i nf or mat i on i sscant y i n pl aces, the changes i n behavi or sad bi ochemstry ascri bed tochroni cal l y i sol ated as opposed t o the maj or i t y of l ong t erm group housed mceare general l y opposi t e i n di recti on to those changes seen f ol l ow ng prol ongedsubj ect i on t o def eat Most studi es i ndi cate that chroni cal l y i sol ated mal emce are more aggr essi ve, showl ower adr enocor t i cal sad adrenal medul l aryf uncti on, i ncreased goaedal f i nct i oa, depressed l evel s of neural nor- epi nephr i neand l owered turnover of neural serotoai n w th respect t o group housed mce Conver sel y, chroni cal l y defeated m ce show decl i nes i n aggress i veness,i ncr eases i n adr enocor t i cal sad adrenal medul l ary f unct i oni ng, and decl i nes i ngonadal f uncti on So f ar as the rntea~ of synt hesi s of brai n catechol amnesare concerned, st rong support f or i sol at i on i nduced changes bei ng opposi te i ndi rect i on to t he effects of def eat are provi ded by t he st udi es reported byModi gh 14h) , who f ound t hat synt hesi s of cat echol am nes i s l ower i n i sol atedthan i n grouped m ce sad that i nt ensi ve f i ght i ng rapi dl 3r accel erated thesynt hesi s of these compounds Taken ae a whol e, the spectrumof changes seeni n i sol ated mal e m ce are l argel y the reverse of those seen f ol l ow ng t heobvi ous stress of def eat and i t seems appar ent t hat i ndi vi dual housi ng s mor erel ated to a l ow rather than a hi gh stress condi t i on

Many of t he di f f erences i s mesa f unct i oni ng of endocri ne gl ands i n mce

8/12/2019 1-s2.0-002432057590017X-main

6/14

19 Contactual I sol ati on and M ce Vol l b, No 2

housed i n di f f erent number s per cage may be a consequence of there bei ngi ncreasi ng numbers of defeated (subordi nate) mce i n these cages as group si zei ncreases see bel ow end 94, 95) The Pact that there are a number of report eddi f f erences i n the l i terature concerni ng the responses of rats and mce toi sol ati on and crowdi ng, may be part i al l y expl ai ned by the observati on that mceare potenti al l y i ndi vi dual l y terr i tori al ani mal s I n thi s speci es one domnantmal e may def end an area (101, 102, 103, 104) , when popul at i on densi t i es are l owsad non- l i near hi erarchi es are of ten f ormed i n smal l cages The rat appears tobe much mor e soci al general l y di spl ayi ng a type of group-t erri tori al i ty 41,105, 106, 107) and rarel y l eadi ng a sol i tary exi stence I t coul d consequent l y beargued that speci es wth di f f erent basi c soci al organi zati ons woul d be unl i kel yto show si ml ar responses to di f f erenti al housi ng

I t has been cl ai med that l aboratory str ai ns of mce may be devel oped f romtwo di f f erent types of natural precursor wth very di f f erent soci al organi zati ons 123 and consequent l y the strai n empl oyed may drasti cal l y al t er the resul ts

one obtai ns when attempti ng to correl l ate hormonal changes and behavi or i n thi sspeci es Mer r y of the physi ol ogi cal and behavi oral vari abl es descri bed i n thi spaper have al so been shown to be prof oundl y i nf l uenced by the strai n of mouseempl oyed e g 44, 45, 46) D ff eri ng earl y experi ence (revi ewed by Brai n, 47i s al so l i kel y to i nf l uence these responses, as wel l as di f f eri ng cage si zes,vari bl e pretreatment housi ng condi t i ons and di f f eri ng durati ona of i sol ati onor groupi ng at di f f erent st ages oP devel opment I t al so of ten appears di f f i cul teven to extrapol ate between wl d ani mal s and ani mal s deri ved f rom wl d pro-geni tors whi ch have been reared i n the l aboratory f or a f ew generati ons, aspronounced behavi oral changes are i nduced by such procedures 108

Meay of the behavi oral end physi ol ogi cal vari abl es consequent upon i so-l ati on and groupi ng i nteract i n a compl ex way I t has been noted, al so, thatthere are si ml ari t i es wth the change i n di recti on oP these vari abl es seen

when domnant and subordi nate i ndi vi dual s are contrasted (39, 89, 90, 92, 109) Ng et e1 110 have al so shown that domnant sad soci al l y wthdrawn mce al sodi f f er w t h respect to neural and adrenal metabol i sm of catechol amnes I t hasconsequentl y been argued that the changes seen on i sol ati on may represent adevi ce whereby a terr i tori al ani mal may be produced As earl y as 1944, Col l i es 111 rel ated much of aggressi ve behavi or i n vertebrates to the concept ofterri tori al i ty Conversel y, terr i tori al i ndi vi dual s tend to be behavi oral l yi sol ated i n that they do not tol erate mature mal e conspeci f i cs on thei rterr i tory and are consequent l y rarel y subj ected t o the stress of defeat As acorr ol l ary i t may be argued that housi ng mal e mce i n smal l cages i n groups,i s a hi ghl y arti f i ci al si tuati on i n that defeated subordi nates are unabl e toescape f rom the terri tory of the domnant Stabl e soci al organi zati ons i nmce tend to be despoti c domnances (95, 112) i n whi ch one mouse i s domnant andthe rest are equal l y subordi nate Thi s, and the Pact that i t has been notedthat pai red aggressi ve mce of ten ki l l thei r partners by repeated attack 95may both be consequences of the ar t i f i ci al i ty of housi ng mce i n smal l groupsi n restri cted cages I t i s i nteresti ng to note that domnance or terri tori al i tymay be a prerequi si te f or good reproducti ve success i n thi s speci es (89, 90,113

I t does appear that a number of mechani sm can be i dent i f i ed whereby themouse may stabi l i se despoti c domnance i n smal l groups or mai ntai n terri tori al -i ty Chroni c el evat i ons of adrenocort i cotrophi c hormone, such as those generat ed i n Subordi nate group- housed or i n mce def eated on another s terr i tory,seem l i kel y to predi spose the ani mal towards show ng l ow l evel s of aggressi ve-ness and demonst rati ng a potenti al i ty f or subordi nate behavi or (114,115, 116,117 Thi s ef ect may have si ml ari ti es wth the acti on of thi s compound oncondi ti oned aw dance reacti ons, i n whi ch the ani mal al so l earns to avoi d anoxi ous st i mul us ( revi ewed i n 118 The acute ef f ects of el evated

8/12/2019 1-s2.0-002432057590017X-main

7/14

Vol 16, No 2 Contactual w ati on and M ne

gl ucocor t i coi da and ACTS appear t o be the reverse, i n t hat such t r eat ment si acreese f i ght i ng behavi or

I f i sol at i on i s not markedl y stressf ul i n adul t mal e mce i t f bl l owathat these ani mal s do not provi de a good model f r the effects of comparabl esi tuat i ons i n men sad pr i mates, and the i nfl uences of drugs on agoni st i cbehavi or may be open to other i nt erpret at i ons than those whi ch have pr edom-nated i s the l i t erature i n recent veers

Suggest ed Approach To I sol at i on Studi en

193

The fact, that l evel s of ci rcul at i ng eadrogene appear to be el evated i sdom nent or i sol at ed mce, means that the aggr essi veness of these ani mal s maybe hi gher than that of def eated mce or the maj ori ty of group- housed ani mal sdue to the st i mul at or y eff ects of such hor mones on thi s behavi or ( 109) I then been al so reported that domnent or i sol ated m ce produce a eubsteace i nthei r uri ne whi ch on agei ng i s aver si ve to i ntr oduced mal e m ce ( 119, 120, 121,122) Thi s al so coul d be a mecheai sm maki ng i t l i kel y that the i ntegri ty ofa terri tory i s mai ntai ned w thout expendi t ur e of l arge amounts of ener gy

I f mce cn i ndeed evi dence t e r r i t o r i a l i t y, even smal l groups of m ce meyshow evi dence of adr enocor t i cal stress a f actor whi ch i nf l uence the res-ponse to actual sad ppteat i el i nf ect i ve agents etc ( 124, 125, 126, 127, 128)

At t empts to r esol ve whether i ndi vi dual housi ng consti tutes a stress i nl aboratory rodents, w l l be pr obabl y ai ded by st udi es i n whi ch di r ect assessment of ci rcul at i ng t i t e r s of gl ucocor t i coi da are made both basal( unstr essed) sad stressed ( f ol l ow ng super i mposi t i on of st eadard str essese g ether def eat etc val ues bei ng obtai ned I t woul d al so seemto bedesi rabl e to at t empt to assess the dynamcs of hormone pr oduct i on and

degradat i on, rather than rel yi ng on absol ut e val ues obtai ned at a f i zed poi nti n t i me I t seems evi dent that, i n many cases, st udi es empl oyi ng organ wei ghtshave l ed to msl eadi ng resul t s

Obvi ousl y, studi es i nvol vi ng depr i vat i on or res t r i ct i on of other sensoryi nput s, normal l y l i t t l e i nf l uenced by i ndi vi dual housi ng, coul d be moat f r u i t -f ul Ani mal s coul d be restr i cted w th respect t o vi sual , ol f actory andul tr asoni c cues f r om members of thei r own speci es There i s much i ndi rectevi dence i mpl i cat i ng the i mpor t ance of these sensory modal i t i es w th respect t obehavi ors r ezampl e, i n many rodents e sense of smel l appears to be ofpar amount i mpor t ance t o t he appeareace of soci al behavi ors O f actory bul babl at i on appears t o suppr ess i ntermal e f i ght i ng i n the r at ( 129) and i n t hemouse (130), al t hough thi s may be rel ated to a neur al rather they a sensorydef i ci t

There i s al so much evi dence that behavi ors are i nf l uenced by sex et er oi d-dependent ol f actory cues ( pheromones) i n many rodent speci es Aggr essi onmodi f yi ng cues f or ezampl e, have been i dent i f i ed i s the uri ne of l abor at or ymce ( 131, 132)

Al t hough i t has been reported that bl i nded ( 133) and congeni t al l y bl i nd( 134) m ce are capabl e of show ng organi zed f i ght i ng behavi or, there have beena number of i ndi cat i ons i n the l i t erature t hat f i ght i ng may be i nf l uenced byvi sual cues Whi te et al ( 135) recorded that f i ghti ng i n mce appeared to bei nf l uenced by the s i ze of t he opponent but th i s i s, of course, not necessari l yrel ated to vi si on

I t has been report ed that ul tr asoni c cues mayr i nf l uence soci al behavi orsi s a vari ety of rodent apeci ea e . g maternal retr i evi ng behavi or i n mce ( 136) ,

8/12/2019 1-s2.0-002432057590017X-main

8/14

19 4 Contactual I sol ati on and Mce Vol 16, No 2

mouse courtshi p 0137) and f i ghti ng 138) and mati ng 139) i s rata Pri or

audi tory ezposure has al so been shown to i nf l uence suscepti bi l i ty to audi o-geni c sei zure i n mce 140) and there have been i ndi cati ons that short endl ong term i sol ated mce behave di f f erentl y i n a si tuati on wt h a di sturbi ngnoi se 61)

An extensi on of thi s approach, empl oyi ng a detai l ed i nvesti gati on ofsensory modal i ti es on responses to di f f erenti al housi ng, coul d hel p to unravelthe compl ex i nterrel ati onshi ps between endocri ne, neural and behavi oral responses i n rodents sad expl ai n some of the di f f erences obtai ned i n apparentl ycomparabl e experi ments

Some tentati ve resul ts concerni ng the ef f ects of ol f acti on on di f ferenti alhousi ng have al ready been made Archer 141) has shown that i sol ated mal e mceexposed to mal e odors f rom uri ne show an i ncrease i n rel ati ve adrenal wei ghtend a depressi on of adrenal ascorbi c aci d compared wth non exposed ani mal s

These f actors show a si ml ar patt ern of chengee, i n mal e mce housed i n proxi mty wthout tacti l e contact when contrasted wth i sol ated mce 142) Nbrestudi es empl oyi ng these consi derati ons woul d seem desi rabl e i f one i s real l ygoi ng to determne the ef f ects of i sol ati on on rodent speci es I t woul d seemteat a resol uti on of thi s probl em s of consi derabl e theoreti cal and practi cali mportance

Ref erences

1 K . E MYER Communs Behav Bi ol . 2 65-87 1968)

2 C. Y YEN R L STARGER end N MLLMAN Arch i nt Phar macodyn ~t79-185 1959)

3 3 CONSOLO 3 GARATTI N and L VALZELLI J Pharm Pharmacol

53 54 1965)

4 J . P SCO1P, Amer Zool 6 683-701 1966)

5 E G ACALONE, M TANSELLA L VALZELLI aad S GARATTI N , B ochemPharmacol ~ 1315-1327 1968)

6 L VALZELLI and S GARATTI A , i n Advances _i n Pharmacol ogy S Garatti nisad P . A Shore, eda) p249, Academc Press, New York 1968)

7 J CHARPENTI ER i n Aggressi ve Behavi our S Garatti ni sad E . B Si gg eds)p86, Excerpts Medi cs Foundati on, Amterdam 1969)

8 E . B SI GG op ci t p143

9 L VALZELLI op ci t p70

B L WELCH and A S WELCH op ci t p188

P . F BRA N and N . W HOWELL Gen comp Endocr 16 149-154 1971)

12 P . F BRA N and A E POOLE, Behavi our 00-110 1974) 13 P . F BRA N and N . W HOWELL, Commons behau H ol ~ -17 1970)

14 A S WELCH sad B L WELCH i n The Physi ol ogy of Aggressi on end Defeat

8/12/2019 1-s2.0-002432057590017X-main

9/14

Vol . 16, i o. 2 Coataatnal I wati oa and Mce 195

B.S El ef theri ou and J . P . Scott , eds p91, Pl enum Press, FewYork 1971)

15 . J . SPSNCSR, J . GRAY nad A DALHOUBE, si ol . Hehav 10 231- 23T 1973

16 . P . F . BRAI 1f Behav Bi ol . Z 349- 357 1972

17 . J . P . SEf i ARD J . Psychol . 3-8 175-197 1945) 18 H. C . Y. YEB, C. A DAY sad E. B SI CG Phermacol oRi st k 173 1962) .

19 E B SI GG C. A DAY ead C ODLOMBO Eadocri nol o 79~84 1966) .

20 W BEVAN W L . BI AOM nnd G. T . LEWS, si ol . Zool . 24 231-237 1951)

21 . J . P. BCOTf , i a Roots of Behavi or E . L Bl i ss, ed p 167, Harper aad RowNew York 9 .

22 L. D CLAAK, op ci t . p179 .

23 E FREDSRi C90N Anat . Rec ~ 509 1949 .

24 J . A KI NG J Genet . Psychol . ~0 151-166 1957

25 E. M Ht J LL L R088 ELLI and C . J . LABGAf t Behav H ol . Q 493-497 1973

26 J . J . CHRI STI AN Amer J . i ol t 81 477- 480 1955

27 J . J C RI STI AN Amer J . ei ol . 182 292-300 1955

28 J . J . CHRI STI AF, Proc . Soc . e~x Bi ol . Med 104 330-332 1960 .

29 J . G VANDEI i HERGH Ani m Behav 8 13- 18 1960) .

30 B . L WLCH and P . H. KLOPFER, Amer . Natur . 56- 260 196 1 .

31 F . H. BENSON ana B . E . >gLEF~RI OU, si ol . tool . ~6 16t- 166 t 963

32 E . D. BAI LEY, Cen . J . Zool . 44 1007-1012 1966)

33 A. S . WLTMA, A. M 3ACKLER, S . B SPARBER nad S . OPERT, Fed Proc 21184 t962)

34 . A. S . i I SLTMAN A. M SACKLER and S . B . SPARBER, Aeros

Med

04-810 t966

35 A H AHTON R. P . BCHFI ARTZend S KRAMER, J . Peychi st . Res 6 211-220 1968 .

36 F. H BRONSON ana v. M c~APMAN Nature Loan 2i 8 483-484 1968 .

37 P F BRAI N and N. W HOWLL, Psychos . Si 22 183-184 1971 .

38 P. F . BRAI N and N. W NOWLL, Gen co Eadocr 16 155- 159 1971

39 P. F . BRAI N Commune behav H ol . 6 115 - 128 1971 .

40 . E . c . GRANT and M R. A CHANC, Aai m Behnv 6 183 - 194 1958) .

41 B. A Anm~mm i n Vi ewpoi nts i n Bi ol orar J . D Ceathy end C.L . Duddi ngton,

8/12/2019 1-s2.0-002432057590017X-main

10/14

196 Contactual I sol ati on and Mce Vol l b, No 2

eds ~ 170, Hutterworths, London 1964

42 J . J CHR STI AN J . A LLOYD and D E DAMS Recent Prog Horen Res 21501-578 1965

43 M C xFer Y, Ecol o~ 48 377- 392 1967

44 AG KARCZMAR sad C L SCUDDER i n Agresai ve Behasi our S Gratti ai andE B S gg eda p209 Excerpts Mdi cs Foundati on Amterdam 1969

45 J . C Le DOUAREC and L BROUSSY, op ci t p281

46 J . R VALE C A VALE and J . P HARLEM Communs Behav Bi ol 6 209-221 1971

47 P F BRA N Commm behau H ol 6 7-18 1971

48 A S WLTMAN A M SACKLER R SCHFI ARTZ and S STROMAA, Experi enti e 23782-784 1967

49 A S WLTMAN A M SACKLER R SC i WARTZ and H OWNS, Lab Ani m Care 18426- 435 1968

50 R SCHWARTZ, A M SACKLER and A S WLTMAN Experi enti a ~0 199-200 1974

51 A M HATCH T BALAZS G S WBERG nd H . C GR CE, Sci eace 142 507 1963

52 A M HATCH G S WBERG Z ZAWDZKA, Z CAAA, I . M ARTH and H C GR CE,Toxi col appl Pharmcol 1 737 - 745 1965

53 G S

WBERG J . M A RTH and H C

GR CE, Food Coamet Toxi col 4 47-55 1966

54 J . T K NG Y . C P LEE and M B VISSCHER Proc Soc H ol Me d 88661-663 1955

55 A M BARBETT and M A STOCKHAM J Eadocr 26 97 - 105 1963

56 M R. A CHANCE, J Pharmcol exptl Therap 8~ 289-296 1947

57 G M K MBRELL PhD Thesi s, Uni e of Tennessee, Knoxvi l l e, 1968

58 B . L WELCH and A S WLCH Rature Lond 218 575 - 577 1968

59 F H BROASON i n Husbandry of Laborato Ani ml s ML Conal ty, ed p513,Academc Press, New York 7

60 w B EssMAA a ~ P ai ol Psychol 66 244- 246 1968

61 P F BRA A, P . G HALEY and . W HOWLL, Commune behau H ol 6 259-270 1971

62 P . F HRA N A W AOWLL aad F H HUCKLEBR DGE, J Endocr 42 xi z-xx 1971

63 J . I KI TAY, M D COYAE, A H SWYGERT and K . E GA AES, Eadocri nol o~ 8~565 - 570 1971

64 J . H GASKI R and J . I K TAY Eadocri aol o~ 8Q 1047-1053 1971

8/12/2019 1-s2.0-002432057590017X-main

11/14

Vol 16, No 2 Coatactual i sol at i on and Mce 197

65 E . M HULL, C J LANGAf t and L ROSSELLI , J comp si ol Psychol 84414-422 1973

66 F DESSI - FI J LGHERI ead C LUPO D PRI SCO Hol l Soc I tal Bi ol Sper 48 894-89T 1972

67 B L WELCH i n Medi cal Aspects of Stress i n the Ml i tary Cl i mate p39,U S Government Pri nt i ng O f i ce, Washi ngton D. C 1965

68 B.L WELCH i n Brai n Functi on C. D Cl emente and D. B Li ndsl ey, eds p150,Uni versi ty of Cal i f orni a Press, Los Angel es 1967

69 B L WELCH aad A S WELCH J Pharm Pharmacol 20 244-246 1968

To M E APRI SOf t aaa J t HnQVrc E f t Fea Proc 121-129 19T2

T1

R

MARCUCCI , E

MU58I N , L

VALZELLI and S

GARATTI N , _ J

Aeurochem 1~53-54 1968

T2 I BAUMEL, J J DE FEO and H LAL, Psychopharm 53-158 196973

S GARATTI N , E GI ACALOf t Eand L VALZELLI , J Pharm Pharmacol 12338-339 1967

74 B L WELCH and A S WELCH Li f e Si 4 1011-1018 1965

75 J P DA VANZO M DAUGHSRTY, R RUCKART and L KANG Psychopharmacol ogi a 210-219 1966

76 J . A GUNf t and M R GURD, J vi ol 53-470 1940

77 E. M GREEABLATT and A C OSTERBERG, J Pharmacol Ezptl Therap115- t1 9 1961

78 B L WELCH and A 9 WELCH J Pharmacol Ezptl Therap 1~1 331-338 1966

79 B . B BROWN Arch I nt Pharmacodyni e 128 391-414 1960

80 8 CONSOLO S GARATTI N and L VALZELLI , J Pharm Pharmacol 594-595 1965

81 F H BROf t SON cad B . E ELEF7~RI OU, Pros Soc ez~ Bi ol Med 118146-149 1965

82 J ARCHER, J Mammal 2T-332 19T0

83 F BRONSOA and B . E ELEFTTERI OU Sci ence ~ 62T-628 1965

84 B. E SLEFTHERI OU and R.L CHURCH Physi ol Behau ~ 323 - 325 1968

85 B.E ELEFTHERI OU and R.L CHURCH Physi ol Behau ~ 9T7-980 1968

86 B.E ELEFTHERI OU i n The Physi ol o~ar p L Aa~easi on g11d Defeat B.EE ef theri ou and J . P Scott , ede p65, Pl enum Press, Neu York 1971

87B E ELEFTSERI OU and R L csuRCH Gen cam Eadocr ~ 263-266 196T

8/12/2019 1-s2.0-002432057590017X-main

12/14

198 Contactual I sol ati on and Mce Vol l b, No 2

88 B . E ELEFTHER OU and R . L CHURCH J Endocr 42 347- 348 1968

89 T D McKI NNEY and J . N PASLEY Gen co Endocr 20 579-583 1973

90 T D McK2NNEY and C DESJ ARD NS, B ol Reprod~ ~ 79 294 1973

91 G D MAENGWYf t - DAMES, D G J OHNSON N B THOA, V L WEI SE and I . J KOPI ft,Pherm co l ogi st 13 303 1971

92 F . H HUCKLEHR DGE, N . W HOWELL and R A DI d4S, Behav B ol 8 785 800 1973

93 B . E ELEFTHER OU R L CHURCH R L NORMAN M PATT NSON and A J ZOLOV CK Physi ol Behav ~ 67 469 1968}

94 P F BRAI N and f t . W HOWELL, P si ol Behav ~ 07 910 1970

95 P . F BRA N and C M EVANS, i s Proceedi ngs of the Fi f th J oi nt Meeti ng ofthe Dutch end Bri ti sh Soci eti es f or Endocri nol o f toordwj kerhoutabstract 10 197

96 H F HAR AW i n Roots of Behavi or E. L B i ss, ed p157 HafnerPubl i shi ng Co . New York 1962

97 E . S VALENSTEIN W R 83 end W C YOUNG J vi ol 48 397 403 1955

98 A A GERALL Ani m Behav 11 274 282 1963

99 A M 3PEVAK, D M QUADAGtO D KNOEPPEL and J . P POGG O Behav B ol

8 63 73 1973

100 E . L BENNETT, M R ROZENZWEI G end M C DAt~DND Sci ence 16~825 826 1969

101 P CROWCROFTand F . P i ~WE, Proc Zool Soc Load 517 531 1963

102 F . P ROWS ana R REDFERN Ana eppl B o1 64 425-431 1969

103 J . H MACKI NTOSH Ani m Behav 18 177- 183 1970

104 J . B CALHOt f t Proc Rte Soc Med 66 80 88 1973

105 J . B CALHOUN 3i Amer 206 139-148 1962

106 J . B CALHOUN Publ i c Heel th Servi ce Publ i cati on t 1008 1962

107 S . A BARNETTsad C . B EVANS, SYmU Zool Soc Lond 4 233 248 1965

108 S . A BARNETTend R . C STODDART J Mamml ~0 321-325 1969

109 P F BRA N Peychon Si 28 260 262 1972

110 L . K . Y NG H M MARSDEN R W COBURN and N B THOA Brai n Res 323 330 i 973

111 N COLLI AS, si ol Zool 12 83 123 1944

112 T B POOLE aad H . D R MOHGAN Ani m Behav 21 788 795 1973

8/12/2019 1-s2.0-002432057590017X-main

13/14

Vol 16, Mo Z Contaotual I wati on and Mce 199

113 J . C DeFRI ES and G f i . McCLEAI YAmer . Bat . 104 408-410 197G

114 P . F . HRAI R, H. W HOWELL and A WOUTERB, i ol . Hehav 6 2T-29 1971 .

115 A I . Lf i SHRBR ead D. K CABDLARD Bew Sci enti st 26-128 1973116 A I . LESHBER, W A WALKER, A. E J OHRSOR, J S . KELLIRG 3 J KRBI SLER and

B . B SVARf i si ol . Behau 1 1 T05 11 1973

117 P . F BRAI R ead A E. POOLf i ~ Behav 2 1- 33 1974

118 . D DeWBD i s ~e HYpothel amus L . Marti ni , M Motte and F . , Fraschi ni ,eds pt, Academc Press, Hew York, 1970

119 R.B J O PESand R . W HOWELL, Ani m Learn Hehav 1 207- 210 1973

120 R.B J oRfi e eaa B . w RowEUL, si al . Hehav 11 35- 38 1973

121. R.B J ORFS and B.W HOWELL, Ani m Behav 21 707-710 1973

122 R.B J OKES ead A W HOWELL, Ani m Hehav 22 187-191 1974

123 G A. VAB OORTMERSSf i R, Behavi our ~8 1- 92 1970

124 D f . DAVI3 and C P . READ Proc . Soc eue . Bi ol Med QQ 269- 272 1958

125 S H VESSEY, Proc Soc . eue Bi ol . Med ~ 252-255 1964

126 w G GLSBI Yand R E. HECKER, si al tool 42 411-416 1969

127

A. R BRAYTOR and P . F

BRAI I QJ

Endocr . 61 zl vi - xl i x 1974 .

128 A. R BRAYTOB and P . F . BRAI N, J . Hel mnthol . 48 99- 106 1974

129 R J . HARDLBR and C . C CHI , si al Behav 8 207-211 1972

130 F. A ROW iand D. A f i DWARI J B si al . Hehav 8 37- 41 1972

131. J . H MACKI RTOSH ead f i C. GRABT, Z Tierpsychol . ~+ 58T 1966 .132 R A. MvGFORD ana R W aow~ L Rature Long . 226 967-968 1970 .

133 P ROPARTZ, Revue Corm. Aai m 2 97 - 102 1967

134 C T LSE and 9 C. BRAKE, Psychos . Si 87- 288 1973

135 M WHI TE, S . MAYO and D. A EDWARDS, Psychon . Si . 16 14- 15 1969

136. R . W BELL, W RI TSCBKE, T. H ORRY aad T. A ZACHMAR, Devel opmentalPsychobiol 4 181-191 1971

137 G WHI TREY, J . R COBLfi M D STOCKTOR and E . F . TI LSOR, J . co i ol .Psychol 84 445-452 1973 .

138 G D 3EWEhL, Rature Lond ~ 12 1967

139 R. J . BARFI BLD ead L . A GEYER, Sci ence 349- 1350 1972140 K. R HERRY, Sci ence 38- 940 1967

8/12/2019 1-s2.0-002432057590017X-main

14/14

200 Contactual i sol ati on and Mce Vol l b No 2

141 J ARCHER J u 39 841 1969

142 J ARCHER Psychon 6i 17- 18 1969

143 P . A BERGER J . D BARCHAS and J VERN K06 DANEI J . I 6 , 14atur e Load . 248424 426 1974

144 K MD GH PsychoPharmacol ogi a Berl . - 17 1973