Cocaine's colocalized effects on synaptic serotonin and dopamine in ventral tegmentum in a reinforcement paradigm

The effect of subcutaneous (SC) cocaine (20 mg/kg) on synaptic concentrations of the biogenic amines, dopamine (DA), and serotonin (5-HT) in Ventral Tegmental Area, (VTA-[A(10)]) was studied in freely moving and behaving rats (rattus norvegicus) with in vivo voltammetry (in vivo electrochemistry). The actual detection of the biogenic amines was on-line and within a temporal resolution of seconds. Simultaneously, the psychostimulant behavior induced by cocaine was studied by infrared photocell beam detection. The results show that cocaine concurrently and significantly increased synaptic concentrations of DA (p < 0.0001) and 5-HT (p < 0.004) in VTA. Serotonin changes were accompanied by a notable oscillatory pattern. Importantly, DA and 5-HT changes in VTA were significantly and positively correlated (p < 0.01). Moreover, psychostimulant behaviors induced by cocaine were significantly increased over control values (p < 0.0001). Psychostimulant behaviors were significantly correlated with concurrently changing synaptic concentrations of DA (p < 0.01) and also with 5-HT to a lesser degree. Additionally, behavioral data indicate that cocaine may exhibit an anxiolytic effect during acute administration because agoraphobic behavior, as shown by increased central ambulatory behavior, was dramatically reduced by cocaine. Summarily, the present findings show that cocaine increased synaptic concentrations of DA in VTA, an action that is correlated with cocaine-induced psychostimulant behavior. The DA-ergic effect appears to be tonically maintained. Furthermore, new findings demonstrate a colocalized, cocaine induced 5-HT-ergic effect in VTA, which keeps pace with cocaine-induced alterations in DA-ergic neurotransmission. Thus, 5-HT may be a relay or a gating mechanism for a DA reward signalling pathway for cocaine.