Regional neurochemical profile following co-administration of apomorphine and buspirone in an animal model of addiction.

Abstract

Although dopamine is the primary neurotransmitter mediating the reinforcing outcomes of abused drugs, serotonin (5-hydroxytryptamine; 5HT) also performs an important function in addiction pathophysiology. Increased dopamine levels in the nucleus accumbens mediate the final effects of various drugs of abuse, regardless of their exceptional preliminary binding sites. Repeated administration of apomorphine has been reported to supersensitize 5HT-1A receptors, and buspirone could attenuate these effects. The present study applied the conditioned place preference (CPP) test to screen apomorphine's reinforcing outcomes and their attenuation by means of co-administration of buspirone. Associated adjustments in 5-HT and dopamine metabolism in various brain regions were monitored using HPLC-EC. Withdrawal from apomorphine administration (1.0 mg/kg on 12 alternate days) brought about reinforcement as observed in the CPP paradigm. Serotonin and dopamine metabolism, mainly in the ventral and dorsal striatum, became additionally altered. The effects propose that desensitization of presynaptic dopamine receptors is concerned in apomorphine-induced reinforcement. Desensitization of somatodendritic 5HT-1A receptors, ensuing in expanded availability of 5HT at 5HT-2C receptors, could attenuate apomorphine-brought about reinforcement. These findings may additionally potentiate the therapeutic applicability of apomorphine.