Repeated cocaine effects on learning, memory and extinction in the pond snail Lymnaea stagnalis

摘要

The persistence of drug addiction suggests that drugs of abuse enhance learning and/or impair extinction of the drug memory. We studied the effects of repeated cocaine on learning, memory and reinstatement in the pond snail, Lymnaea stagnalis. Respiratory behavior can be operantly conditioned and extinguished in Lymnaea, and this behavior is dependent on a critical dopamine neuron. We tested the hypothesis that repeated cocaine exposure promotes learning and memory or attenuates the ability to extinguish the memory of respiratory behavior that relies on this dopaminergic neuron. Rotating disk electrode voltammetry revealed a K-m and V-max of dopamine uptake in snail brain of 0.9 mu mol l(-1) and 558 pmol s(-1) g(-1) respectively, and the IC50 of cocaine for dopamine was approximately 0.03 mu mol l(-1). For operant conditioning, snails were given 5 days of 1 h day(-1) immersion in water (control) or 0.1 mu mol l(-1) cocaine, which was the lowest dose that maximally inhibited dopamine uptake, and snails were trained 3 days later. No changes were found between the two groups for learning or memory of the operant behavior. However, snails treated with 0.1 mu mol l(-1) cocaine demonstrated impairment of extinction memory during reinstatement of the behavior compared with controls. Our findings suggest that repeated exposure to cocaine modifies the interaction between the original memory trace and active inhibition of this trace through extinction training. An understanding of these basic processes in a simple model system may have important implications for treatment strategies in cocaine addiction.