In vivo electrochemical studies of gradient effects of (SC) cocaine on dopamine and serotonin release in dorsal striatum of conscious rats

Abstract

Cocaine (20 mg/kg) was administered subcutaneously (SC) to conscious male Sprague-Dawley rats after exploration in a novel chamber. (SC) cocaine was studied for its influence on in vivo dopamine (DA) and serotonin (5-HT) release in dorsal striatum (STr), with a further study of an anterior-posterior dorsal subdivision in a range of ± 400 μm. Semiderivative voltammetry, a circuit for in vivo electrochemical biotechnologies, was used in combinatiion with a stearate microelectrode to concurrently detect in separate electrochemical signals the elctroactive species for DA and 5-HT in dorsal STr. The temporal resolution for detection was in the order of seconds. Concomitantly, cocaine-induced pcyhostimulant behaviors were studied with infrared photobeam detection. Psychostimulant behaviors classically thought to depend on DA—that is, hyperactivity (increased locomotor activity or ambulations), rearing, and finally stereotypy (fine movements of grooming and head bob)—and a 5-HT-ergic behavior, central ambulations, were monitored. The results showed that (SC) cocaine significantly ( p < 0.0001) increased DA release in dorsal STr, whereas the overall effect of (SC) cocaine on 5-HT release was a significant increase ( p < 0.0001) followed by an overall small (13%) but statistically significant decrease ( p < 0.05). A dramatic cocaine-induced gradient effect on 5-HT release was seen in anterior-posterior dorsal STr, where 5-HT release was significantly ( p < 0.0001) increased throughout the entire time period of study. Classically DA-dependent behaviors were significantly and positively correlated with increased DA release in dorsal STr and anterior-posterior dorsal STr( p < 0.001) in the 4-h period of study. However, 5-HT release after cocaine in the anterior-posterior dorsal STr was significantly and positively correlated with the classically DA-dependent behaviors as well ( p < 0.001), implicating a role for 5-HT in the effectuation of cocaine-induced psychostimulant behavior. Generally, the 5-HT-ergic response to cocaine was enhanced before the DA-ergic response. Therefore, the data show that 5-HT as well as DA plays a role on the underlying mechanism of action of cocaine in dorsal STr. The data suggest that 5-HT may play a compensatory or adaptive role in the modulation of cocaine-induced nigrostriatal DA-ergic regulation.