ELECTROPHYSIOLOGICAL EFFECTS OF COCAINE IN THE RAT NUCLEUS-ACCUMBENS - MICROIONTOPHORETIC STUDIES

The nucleus accumbens (NAc) is intricately involved in maintaining coc aine self-administration. Cocaine inhibits the firing of most NAc cell s due to its ability to prevent the reuptake of dopamine (DA) and 5-hy droxytryptamine (5-HT), both of which predominantly inhibit NAc cell d ischarge in vivo. The present studies investigated the roles of DA and 5-HT in the effects of iontophoretically applied cocaine. Most NAc ce lls exhibited negative/positive waveforms (Type I cells). These cells were significantly more sensitive to cocaine than Type II cells (posit ive/negative waveforms), apparently due to differences in the actions of 5-HT. Whereas DA was equipotent at inhibiting Type I and Type II ce lls, 5-HT inhibited Type I cells but, primarily excited Type II cells. Thus the ability of cocaine to potentiate the effects of both DA and 5-HT resulted in a pronounced inhibition of Type I cells, whereas the 5-HT-mediated excitation of Type II cells appeared to reduce DA-mediat ed inhibition. Combined administration of selective DA (GBR 12909) and 5-HT (fluoxetine) uptake inhibitors was required to mimic the effects of cocaine on Type I and Type II NAc cells. Acute depletion of DA (86 %) produced by alpha-methyl-p-tyrosine (AMPT) significantly reduced th e inhibitory effects of cocaine on all NAc cells. Acute depletion of 5 -HT (74%) produced by p-chlorophenylalanine (PCPA) significantly reduc ed the inhibitory effect of cocaine on Type I cells, but it significan tly enhanced the inhibition of Type II cells. Simultaneous reduction o f DA and 5-HT levels produced a significantly greater reduction of coc aine-induced inhibition of Type I neurons than did AMPT or PCPA alone. These findings are discussed in relation to proposed roles of DA and 5-HT in cocaine self-administration.