Dose-related effects of the acetylcholinesterase inhibitor tacrine on cocaine and food self-administration in rats

Rationale Acetylcholine (ACh) is involved in brain reward and learning functions and contributes to opiate- and psychostimulant-motivated behaviors. Tacrine is a centrally acting, reversible cholinesterase inhibitor that also inhibits monoamine oxidase (MAO) and blocks reuptake of dopamine (DA) and serotonin. Objectives To determine the effects of pretreatment with tacrine on self-administration of cocaine and nondrug reinforcers. Materials and methods Male Wistar rats were trained to self-administer cocaine under a fixed-ratio-5 (FR-5) schedule during 2-h multiple-component sessions in which 0.1, 0.2, and 0.4 mg/kg per injection of cocaine were each available for 40 min. Other animals self-administered 45 mg food pellets under FR-30 or 20% Ensure (liquid food) under FR-5 in amounts of 30, 60, or 120 mu l. Vehicle or tacrine was administered as single intravenous doses 20 min before self-administration of cocaine, food pellets, or liquid food. Results Although pretreatment with 0.032 mg/kg of tacrine increased self-administration of food pellets, pretreatment with higher doses of tacrine attenuated self-administration of cocaine, food pellets, or liquid food. Tacrine's ED50 value for attenuating self-administration of 0.1 mg/kg per injection of cocaine was more than sixfold lower than values for attenuating liquid food- or food pellet-reinforced behavior. However, ED50 values for attenuating self-administration of higher doses of cocaine were similar to those observed for 30 or 60 mu l of liquid food. Conclusions Tacrine can selectively attenuate self-administration of low-dose cocaine, but its effects on higher doses of cocaine are similar to its ability to decrease self-administration of nondrug reinforcers.