Enhanced accumbal dopamine release following 5-HT2A receptor stimulation in rats pretreated with intermittent cocaine

This study was conducted to determine whether dopamine (DA) release in the nucleus accumbens (NACC) following 5-HT_2A receptor stimulation is potentiated by intermittent cocaine. Rats received daily injections of either saline or cocaine (30 mg/kg, s.c.) for 14 days. At the 7th day after withdrawal, microdialysis was performed in the NACC. Infusion of (±)-1-(4-iodo-2,5-dimethoxyphenyl)-2-aminopropane (DOI, 50 μM), a 5-HT₂ receptor agonist, into the NACC produced greater and longer-lasting increases in extracellular DA in the rats pretreated with cocaine than in the rats pretreated with saline. The DOI-induced increases in NACC DA were attenuated by co-perfusion with ketanserin (50 μM), a 5-HT_2A receptor antagonist. The results are consistent with the concept that intermittent cocaine may cause enhanced sensitivity of 5-HT_2A receptors within the NACC.