Drugs of abuse as memory modulators: a study of cocaine in rats.

RATIONALE: It has been proposed that drugs of abuse reinforce behavior partly, or wholly, because they facilitate learning by enhancing memory consolidation. Cocaine can clearly serve as a reinforcer, but its effect on learning has not been fully characterized. OBJECTIVES: To explore the effects of different regimens of pre- and post-training cocaine administration on win-stay and object learning. METHODS: Cocaine naïve and cocaine pre-exposed (30 mg/kg/day, × 5 days followed by 7 days drug-free) male Sprague-Dawley rats received cocaine (0, 1, 2.5, 7.5, or 20 mg/kg, i.p.) immediately following training on a win-stay task in a radial maze or following the sample phase of an object learning task. Win-stay performance was also assessed in tests of extinction and after a set shift. RESULTS: Post-training cocaine did not improve accuracy on the win-stay task and produced performance deficits at 20 mg/kg. These deficits were attenuated by prior cocaine exposure. There was indirect evidence of facilitated learning in extinction and set shift tests, but the effective dosage was different (2.5 and 7.5 mg/kg, respectively). Post-training cocaine produced dose-dependent improvements in object learning. CONCLUSION: Post-training cocaine administration can facilitate learning, but this effect is highly dependent on the dose and the type of task employed.

Effect of post-training administration of cocaine, diazepam and their combination on a win-stay task.

According to the memory-enhancing hypothesis of addictive drugs, post-training administration of cocaine should enhance consolidation and thus facilitate learning. This hypothesis has not been tested in appetitive tasks reinforced by sucrose. The current study assessed the effect of post-training cocaine administration on the acquisition of a win-stay task, and modulation of this effect by co-administration of diazepam. Male Sprague-Dawley rats (n=63) were trained for 5 days on a win-stay task performed on an 8-arm radial maze, and were administered cocaine (0, 2.5, 7.5 or 20mg/kg), diazepam (1mg/kg), or cocaine (7.5mg/kg)+diazepam (1mg/kg) immediately following each training session. Post-training cocaine caused dose-dependent impairments that appeared linked to the development of cocaine-induced sucrose taste avoidance and/or cocaine-induced anxiety. When it was attempted to modify these learned side effects of cocaine by co-administration of diazepam, it was observed that the drug combination slowed task completion and reduced overall number of nose pokes. These findings suggest that post-training cocaine can alter behavior on appetitive tasks through learned motivational deficits rather than through a selective action on memory consolidation. The implications for the memory-enhancing hypothesis of addictive drugs are discussed.