Self-administration of cocaine increases the release of acetylcholine to agreater extent than response-independent cocaine in the nucleus accumbens of rats

Rationale: The neurochemical effects of psychostimulant exposure may depend on how these drugs are encountered. A useful method for examining this iss ue is to compare neurotransmitter release following response-dependent, or self-administered, drug exposure and response-independent exposure. Objecti ves: This experiment examined the effect of active and passive cocaine admi nistration on acetylcholine (ACh) efflux in the shell region of the nucleus accumbens (NAc) in rats. Methods: One group of rats (CSA: cocaine self-adm inistration) was trained to lever-press for intravenous infusions of cocain e (0.42 mg/kg per infusion) on a fixed-ratio-1 schedule of reinforcement. C ocaine infusions were accompanied by the onset of a stimulus light that sig naled a 20-s time-out period. Control rats received intravenous cocaine (co caine non-contingent: CNC) or saline (SAL) in a manner that was not conting ent upon their behavior, Drug infusions in these groups were determined by the lever-press behavior of the animals in the CSA group, i.e. they were yo ked to rats in the self-administration group such that CNC animals received equal amounts of cocaine as CSA rats. Animals received cocaine or saline i n 3-h sessions for 13 consecutive days before testing. On day 14, extracell ular ACh was measured in 15-min intervals before, during and after a 3-h se ssion of cocaine exposure using unilateral microdialysis probes located in the NAc shell coupled with HPLC. Results: ACh efflux was significantly incr eased above baseline in both groups of rats that received cocaine but CSA r ats had significantly higher ACh levels during the self-administration peri od compared to their yoked counterparts, In addition, ACh efflux remained e levated ion ger in CSA animals relative to CNC rats following cessation of cocaine exposure. Conclusions: These results demonstrate that ACh interneur ons in the NAc shell are responsive to cocaine exposure. In addition, these findings suggest that the manner in which the drug is administered (i.e. e ither by active self-administration or passive exposure) may be relevant to the magnitude of the neural response.