A 24-h access I.V. self-administration schedule of morphine reinforcement and the estimation of recidivism: Pharmacological modification by arecoline.

Central cholinergic neurons are known to play a role in the pharmacological actions of opiates. The purpose of the study was to determine whether the muscarinic receptor agonist arecoline, administered during morphine self-administration, would mitigate the subsequent return to self-administration behavior. Rats self-administered increasing concentrations of morphine in operant chambers according to a schedule that permitted unlimited access to lever-activated i.v. infusions on a continuous 24 h basis from 10 to 14 days. Abstinence was induced by discontinuation of the morphine solution and mild withdrawal symptoms were evident from 14 to 74 h. Thereafter the rats remained in their home cages for a 6-week period of protracted abstinence. They were then returned to the operant chambers where lever responding had no reward consequence. The cholinergic muscarinic agonist arecoline was administered twice daily (0.25 or 1 mg/kg, s.c.) throughout the self-administration schedule of morphine. Arecoline treatment partly decreased the self-administration of morphine, it prevented the abstinence-induced decrease in body weight, and it reduced lever responding after protracted withdrawal (by 56%). In animals already dependent on morphine, arecoline failed to alter ongoing self-administration behavior, but responding induced by lever reinstatement 6 weeks after withdrawal was significantly reduced (by 33%). There was a significant relationship between the degree of self-administration activity and the degree of lever responding during reinstatement after protracted abstinence. The results of this study support the role of cholinergic systems in self-administration behavior and context-induced post-withdrawal drug seeking.