Real time detection of acute (IP) cocaine-enhanced dopamine and serotonin release in ventrolateral nucleus accumbens of the behaving Norway rat

Cocaine (10 mg/kg), administered intraperitoneal (IP), was studied for its effects on dopamine (DA) and serotonin (5-HT) release in ventrolateral nucleus accumbens (vlNAcc) of conscious and behaving male, virus-free, Sprague-Dawley rats with in vivo electrochemistry (voltammetry). Miniature stearate probes detected DA and 5-HT release, on line and within a temporal resolution of seconds. Psychostimulant behaviors, in the form of four behavioral components (i.e., the classically DA-dependent behaviors of locomotor activity [ambulations], rearing, and stereotypy, and a 5-HT-ergic behavior, central ambulations) were studied concurrently with infrared photobeam detection. The results show that (IP) cocaine significantly increased vlNAcc DA release (p < 0.0001) and 5-HT release (p < 0.0012). Each of the four parameters of cocaine-induced psychostimulant behavior was concurrently and significantly increased as well (ambulations: p < 0.0001; rearing: p < 0.0008; stereotypy: p < 0.0004; central ambulations: p < 0.0082). Moreover, exactly coincident data points for DA and 5-HT release occurred 10 and 40 min after (IP) cocaine administration. Cocaine-induced DA and 5-HT release were highly and positively correlated during the first hour of study (p < 0.01). As expected, increased DA release in vlNAcc after cocaine administration was significantly and positively correlated with classically DA-dependent behaviors (first- and second-hour effects) (p < 0.01) and with the 5-HT-ergic behavior, central ambulations (p < 0.01). Also, cocaine-induced 5-HT release was significantly and positively correlated with 5-HT behavior (p < 0.01). However, not as expected, classically DA-dependent behaviors were more positively correlated with cocaine-induced 5-HT release in vlNAcc throughout the two-hour period of study. Thus, the present findings show that 5-HT is a comediator with DA in the cocaine response in vlNAcc. Importantly, 5-HT may signal the known DA response to cocaine.