Effects of extended cocaine access and cocaine withdrawal on choice between cocaine and food in rhesus monkeys.
Chronic drug use may lead to sufficient drug intake to produce dependence and the emergence of abstinence signs during withdrawal. Although withdrawal can increase the reinforcing effects of some drugs (eg opioids), the impact of withdrawal on the reinforcing effects of stimulants like cocaine is less clear. This study used a novel cocaine vs food choice procedure to examine the relative reinforcing strength of cocaine before, during, and after exposure to graded levels of extended cocaine access. Responding in four rhesus monkeys was maintained by cocaine (0-0.1 mg/kg/injection) and food delivery under a concurrent-choice schedule during daily 2-h sessions. Under baseline conditions, cocaine maintained a dose-dependent increase in cocaine choice. Subsequently, subjects were exposed to and withdrawn from periods of extended cocaine access, which was accomplished by implementing daily 21-h supplemental sessions of cocaine self-administration in addition to daily choice sessions. During supplemental sessions, cocaine (0.1 mg/kg/injection) was available under a fixed-ratio 10/time-out X schedule, and the duration of the time-out was varied from 30 to 7.5 min. Cocaine intake increased 10-fold to >11 mg/kg/day during exposure to supplemental sessions with the shortest post-injection time-out. However, parameters of cocaine choice were not significantly affected either during or after extended cocaine access. These results do not support the hypothesis that cocaine withdrawal increases the reinforcing strength of cocaine. This differs from results with the opioid agonist heroin and suggests that withdrawal may have different functions in the maintenance of opioid and stimulant abuse.
Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA 23298, USA.
Matthew L
ML
Banks
S Stevens
SS
Negus
D000818:Animals; D002755:Choice Behavior / Q000187:drug effects*; D003042:Cocaine / Q000008:administration & dosage / Q000009:adverse effects*; D003216:Conditioning, Operant / Q000187:drug effects*; D004195:Disease Models, Animal; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005502:Food; D005518:Food Preferences / Q000187:drug effects; D008253:Macaca mulatta; D008297:Male; D012055:Reinforcement Schedule; D012646:Self Administration; D013375:Substance Withdrawal Syndrome / Q000523:psychology*; D013997:Time Factors
D018765:Dopamine Uptake Inhibitors; D003042:Cocaine