In vivo electrochemical studies of gradient effects of (SC) cocaine on dopamine and serotonin release in dorsal striatum of conscious rats.
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 microns. Semiderivative voltammetry, a circuit for in vivo electrochemical biotechnologies, was used in combination with a stearate microelectrode to concurrently detect in separate electrochemical signals the electroactive species for DA and 5-HT in dorsal STr. The temporal resolution for detection was in the order of seconds. Concomitantly, cocaine-induced psychostimulant behaviors were studied with infrared photo beam 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 in 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.
Broderick
P A
PA
Department of Pharmacology, City University of New York Medical School, New York 10031.
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003042:Cocaine / Q000494:pharmacology*; D003470:Culture Media; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004563:Electrochemistry; D008297:Male; D008839:Microelectrodes; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism*; D013268:Stimulation, Chemical
D003470:Culture Media; D012701:Serotonin; D003042:Cocaine; D004298:Dopamine