66

123

PROPERTIES OF PHENCYCLIDINE BINDING SITES IN MOUSE CEREBRAL CORTEX MEMBRANES DURING DEVELOPMENT Pirjo Saransaari and Simo S. OJa, Tampere Brain Research Center, Department of Biomedical Sciences, University of Tampere, Finland The dissociative anesthetic phencyclidine (PCP) is bound to sites associated with the NMDA subclass of excitatory amino acid receptors in the brain. The PCP binding sites were now characterized by measuring the binding of a labeled PCP analog, TCP (N-(l-[2-thieny~ cyclohexyl) piperidine) to cerebral cortex membranes isolated from adult and developing mice. The frozen and thawed membranes were incubated in i0 mM Hepes buffer, pH 7.4, at 25 °C for 45 min and then rapidly filtered onto glass fiber filters presoaked in polylyslne with subsequent washings with cold buffer. TCP binding was saturable in the studied concentration range of 2 to 200 nM, exhibiting one binding component in both adult and developing brain. The maximal binding capacity decreased during postnatal development, whereas the binding constant was not significantly altered. Glycine potentiated the binding concentratlon-dependently in the adult cerebral cortex, whereas only a small stimulation was discernible in 7-day-old mice. NMDA, L- and D-glutamate also enhanced TCP binding; the effects being again somewhat smaller in the developing brain. Taurine and 8-alanine stimulated TCP binding but only at concentrations higher than those of glyclne. On the other hand, taurine had no effect on the glutamate-, NMDA- or glycine-potentlated TPC binding. The differences in the properties of cortical PCP binding sites in the developing and adult brain are likely to affect regulation of the function of NMDA receptors. Supported by the Emil Aaltonen Foundation, Finland.

124

FLUCTUATION ANALYSIS OF THE DOMOIC ACID EVOKED CU!~RENTS IN CEREBELLAR NEURONS

Marina Sciancalepore, Zygmunt Galdzickl, Zheng Yin and Oscar Moran

Scuola Internazionale Superlore di Studl Avanzati (SISSA), Strada Costiera ii, 1-34014 Trieste, Italy.

Domoic acid is a dlcarboxilic aminoacld that acts as an agonist on the glutamic acid receotor and

has been recently involved in neurotoxic eDisodies. When domoic acid is applied to cerebellar

granule cells by pressure ejection, macroscopic currents were observed using the whole-cell patch-

clamp technique. Power spectra were calculated from currents recorded during 30 sec aDDllcation

of domoic acid. Spectra were fitted with a single lorenzlan function, giving a characteristic

time constant of 1.7±0.3 msec (mean±s.d., n=lO). Tingle channel conductance of 4.0±0.5 pS was estimated by the extrapolation of the lorenzlan 9unction to 0 frequency. Time constant and

unitary events of the domoic acid activated currents were very similar to those observed on Wainic

acld activated current and different to those obtained with NMDA and glutamic acid.

125

MODULATION OF DOPAMINERGIC TRANSMISSION IN RAT CORTEX BY EXCITATORY AMINO ACIDS

Giovanni Selvaggi °, Paolo Bongioanni, Emilio Fiore, Scuola Superiore di Studi Uni

versitari e di PerFezionamento(S.S.S.U.P.)-S.Anna,Pisa;oUniversity of Turin,ITAL~

In the present study the effects o£ bilateral infusion of excitatory amino acids

(EAA) into the medial Frontal rat cortex on dopamine(DA) metabolism have been eva

luated. Local injection of AP-5 and AP-7, two N-methyl-D-aspartate(NMDA) recepto~

antagonists, increased the medial frontal cortex 3,4-dihydroxyphenylacetic acid

(DOPAC) amount and the DOPAC/DA ratio. The infusion o£ APB,or glutamic acid die-

thylester(GDEE), two quisqualate receptor antagonists, or gamma-glutamyl-aminome-

thyl sulphonate, a quisqualate/kainate receptor antagonist, Failed to influence

the DOPAC/DA cortical ratio or the DA utilization in the rat medial Frontal cortex.

These Findings are consistent with the hypothesis of NMDA receptor involvement in

the inhibitory regulation o£ dopaminergic transmission in rat medial Frontal cor-

tex.The results are discussed in terms of interrelationships between the EAA-er~c and DA-ergic neurotransmitter systems.