ELEVENTH ALCOHOLISM FORUM 7ol

7 MARIHUANA AND ITS INTERACTION WITH ALCOHOL. Marie Perez-Reye~ M.D., Dept. of Psychiatry & Center for Alcohol Studies, University of North Carolina, Chapel Hill, NC 27514.

The use of alcohol and marihuana is widespread among young people, and often they use the two drugs concomitantly. The purpose of the present study was to investigate the effects of the interaction between the two drugs on the performance of skills necessary to drive an automobile or to operate machinery with precision. Six male, healthy, paid volunteers~ familiar with the use of alcohol and marihuana were tested at weekly intervals or longer, in a single-blind, cross-over de- sign with the following conditions; placebo-placebo; placebo- low-alcohol; placebo-high-alcohol; raarihuana-placebo; marihuana-low-alcohol; and marihuana-hlgh-alcohol. The two doses of alcohol used were 1 or 2 ml/kg of I00 proof vodka (0.42 or 0.85 g/kg of alcohol) diluted to 300 ml with orange juice. Fifty nd of the mixture was administered every five minutes for 30 minutes. The single dose of marihuana used in the study was administered in the form of a 2.45% THC content NIDA marihuana cigarette. The following parameters were measured: the subjective rating of marihuana "high" or of alcohol intoxication; the heart rate acceleration; the plasma concentration of THC and its principal metabollte (9-carboxy THC); the performance on the Self-Evaluation Driving Impairment (SEDI) task; and on two short-term memory tests (the word recall and the Sternberg's test). The re- sults indicated that the effects on performance of the con- comitant administration of alcohol and marihuana were additive

8 GABAERGIC MECHANISMS 1N THE INFERIOR COLLICULUS AND ETHANOL WITHDRAWAL SEIZURES. G e r a l d F r y e , Thomas HcCown & George Bree se , Texas A & M Univ. Col . o f Med., C o l l e g e S t a t i o n , TX & Univ. o f N. C a r o l i n a , Sch. o f Hed . , Chapel H i l l , NC. Wi thdrawal a u d i o g e n i c s e i z u r e s a r e s u p p r e s s e d by i n j e c t i o n of GABA a g o n i s t s i n t o the i n f e r i o r c o l l i c - u l u s , whi le b i c u c u l l i n e ( i n naive r a t s ) i nduces s e i z u r e - l i k e r e s p o n s e s (Frye e t e l . , J . Pha rmaco l . Exp. Ther . 2 2 7 : 6 6 3 - 6 7 0 , 1983) . In the p r e s e n t r e p o r t O.OlnHoles of b icucu l l l ne i n f u s e d b i l a t e r a l l y ( 0 . S u l / S m i n ) i n t o the i n f . c o l l i c u l u s r a p i d l y evoked r u n n i n g s e i z u r e s in 4 . 5 + 0 . 3 min . O t h e r CABAergic drugs, p i c ro tox in ( lnHole) & Re 5-3663 (10nHole) a convulsant benzodiazepine, also induced seizures w i th in 5 min. Ey cont ras t , drugs not re lated to GABA, strychnine (lOnMole), carbechol (lOnMole) & ka lu ic acid (0.1nHole) also caused running seizures a f t e r c o l l l c u l a r i n f u s i o n but the r e s p o n s e s were d e l a y e d an a v e r a g e of 8 -10 min a f t e r the s t a r t of the i n f u s i o n . In a n o t h e r s t u d y e l e c t r o l y t i c l e s i o n s o f the m e d i a l g e n i c u l a t e body, a ma jo r c o r t i c a l r e l a y p o i n t f o r o u t p u t from the c o l l l c u l u s , f a i l e d to c o n s i s t e n t l y b l o c k e t h a n o l w i t h d r a w a l s e i z u r e s in dependent r a t s . These d a t a f u r t h e r suppor¢ a r o l e f o r GARAergic h y p o a c t i v i C y in the i n f e r i o r c o l l i c u l u s in the g e n e s i s o f audlogenlc s e i z u r e s d u r i n g e t h a n o l w i t h d r a w a l . Suppor t ed by PHS AA06322 & AA02334 and NCARA 8207.

9 FATTY ACID-DEPENDENT ETHANOL METABOLISM IN THE ISOLATED, PERFUSED RAT LIVER. g.A. Handler and R.G. Thurman, Dept. of Pharmacology, Ur~v. of North Carolina at Chapel Hill, Chapel Hill, NC 27514.

The peroxisomal P~oxidation of fat ty acids produces H?O 7 (Lazarow, P.B., J. Biol. Chem. 253:1522, 1978). The purpose of Thi~ study was to determine if the HTO~ from I~-oxidation could support ethanol metabolism via the cat%lEse-H202 pathway. Livers from fasted /Female rats were perfused m a reclrculating system contammg ethanol (20-3~ mM). Ethanol was determined enzymati- cally in samples taken every 30 mmutes and rates of ethanol uptake were calculated after correction for minimal losses of ethanol by vaportzatton. Control rates of ethanol uptake of 89 + 16 IJmol/g/h were decreased to B + 2 pmol/8/h by 4-methylpyrazole (4 raM), an inhibttor of aJcoh~ dehydrogenase. Ethanol also decreased the steady-state level of catalase-H~O~ determined spectrophotometrically (~60-640 nm) by transmissioB through a lobe of the liver. Oleate (1 raM) tn the presence of 4-methylpyrazole mcreased the rate of ethanol uptake to 72 + 20 iJmoUg/h and increased the steady-s~ate level of catalase-H~(~. Pretreatment of rats for 1.~ h w~th ~-amino-l,2,4-triazole (1 ~ /~ ) , an inhibitor of catalase, prevented the spectrophotometric changes in the catalase-H20~complex caused by ethanol and oieate and blocked the oleate-st£f~ulated ethanol uptake by about 73%. These data are consistent with the hypothesis that the peroxisornal 13-o~idation of fatty acids can produce suf~tcient H20 ~ to peroxidize ethanol at high rates wa catalase-H202 m the per'~used liver (AA-01624 and GM-07040).

10 PRENATAL I~po,.~RR TO ETHANOL ALTER8 HZPPOCJMPAL FUNCTION° H..q. SvaPt.m, mldae . C.P. 3utnh. £ .C. Bpa,,,,.~n ~ V . I . W41~-~n, Duke Univ. and VA Hedleal Centers, Durhaa, WC 27705.

The htppoosmpue As tbouKht t o p l a y a n ~ p o r t a n t r o l e i n l eamrLt~ and a ~ o r y . Both p r e n a t a l and a d u l t e x p o s u r e t o e t h a n o l have been Bbo~m t o t u p a i r learnLz~ and a l t e r h£ppoomnpal e t r u o t u P e a l K n l F t o e n t l y , bu t ~ ,~o tAona l o o r P e l a t e a o f t h e s e a n a t o m i c a l o h a ~ e n have not been i n v e a t i K a t e d p h y e L o l o g i e e l l y .

P r e g n a n t L o ~ - E v a n 8 r a t a were f ed l i q u i d d i e t ~ w i t h 35~ o f o a l o r / e e ae e / a b e t e t h a n o l o r auoPoae . Na le o f f e p r l ~ ware • ae r i f i ond a t 90-110 daye; 625 u e hippooaBl~Ll s l i ces were p r e p a r e d I n e t a n d a r d t a a h $ o n . A b l l n d e d ex la tner reoorded CA3 e x t m a o e l l u l a r f i e l d p o t e n t i a l s evoked by s t l a u l a t £ o n o f p e r f o r e n t p a t h , d e n t a t e I f f rue , o r a r e a C11, Rate exposed p r e n a t a l l y t o a l o o b o l a p p e a r e d t o r eepond a b n o r m a l l y t o buth orthedroLtc and ant/dromic ac t / va t / on . The m a t d e f i n i t e abnormal i ty was s een fol lowLnK paJJ.ed a t L a u l a t l o n in a . radiatum o f Or1, NOrmLt r a t e shoeed o o n v u t t o n a l p a i r e d - p u l s e P o t e n t i a t i o n o f t h e o r t b o d e o l d e o o a p o n e n t . In ethanol-exposed ra ta , ;mired a t t m l a t / o n evoked a buret o f a u l t i p l e populat /on ap/kna. These resu l ta pr~v/de evldenoe ~hat a n i m a l s exposed t o e t h a n o l I n u t e P o a n ~ / ~ r a F u n o t / o n a l d e f t o l t In t h e h£ppooanpun whtoh p o r e / a t e i n t o a d u l t h o o d .

Supported by N.C. APA Grant 8305.