ABSTRACT
Neuronal substrates that mediate the conditioned effects of cocaine have not been well characterized. To examine dopaminergic mechanisms, three antagonists were tested for their capacity to inhibit the expression of conditioned locomotor activity and conditioned place preference in rats. Antagonists were also assessed against acute cocaine-stimulated locomotor activity for comparison. For locomotor activity conditioning, six conditioning sessions were conducted over a 10-day period. Paired rats received 10 mg/kg cocaine prior to activity sessions and saline after; unpaired controls received saline prior and cocaine after. For place preference conditioning, eight conditioning sessions were conducted over a 13-day period; rats received 10 mg/kg cocaine while restricted to one of two distinct chambers and, on alternate days, they received saline in the other. Antagonists (haloperidol, raclopride and SCH23390; 0.03-0.1 mg/kg) were given only on test days for conditioned effects. All three antagonists significantly and dose-dependently attenuated the direct stimulatory effect of cocaine. SCH23390 showed a tendency to reduce the expression of conditioned locomotor activity, and only haloperidol blocked the expression of conditioned place preference. Thus, direct and conditioned stimulant effects of cocaine were shown to be differentially sensitive to dopamine receptor blockade. Further, conditioned stimulant effects differed from conditioned reinforcing effects in this regard.
Subject(s)
Cocaine/pharmacology , Conditioning, Operant/drug effects , Dopamine Antagonists/pharmacology , Dopamine Uptake Inhibitors/pharmacology , Motor Activity/drug effects , Animals , Benzazepines/pharmacology , Dopamine D2 Receptor Antagonists , Dose-Response Relationship, Drug , Haloperidol/pharmacology , Male , Raclopride/pharmacology , Rats , Rats, Sprague-Dawley , Receptors, Dopamine D1/antagonists & inhibitorsABSTRACT
RATIONALE: Classical conditioning has been proposed to account for the hyperactivity observed in drug-free rats when placed in an environment previously paired with cocaine administration. However, an alternative explanation is that hyperactivity results from an inability of rats to habituate to the environment under the influence of cocaine. OBJECTIVES: In this study, preconditioning exposure to the test environment was increased from one session (standard procedure) to seven (modified procedure) to test the "antihabituation" hypothesis. METHODS: After preconditioning exposure, six conditioning sessions took place over a 10-day to 13-day period. Paired rats received 10 mg/kg cocaine i.p. prior to activity sessions and saline i.p. upon return to the colony room. Unpaired rats received saline prior to and cocaine after activity sessions. Time-off rats were withheld from the activity boxes, but were subject to all other procedures during conditioning. On the test day, all rats received saline prior to activity sessions. RESULTS: In the standard procedure, paired rats exhibited significantly greater activity than unpaired rats on the test day, consistent with previous reports. In the modified procedure, mean activity (all rats) decreased between the first and last preconditioning sessions. Still, the paired group exhibited greater activity than the unpaired group on the test day, suggesting that a conditioned stimulant effect developed in habituated rats. Activity in the time-off group did not significantly differ from the unpaired group demonstrating the habituation had not dissipated over this time period. CONCLUSIONS: These results support the conclusion that hyperactivity observed on the test day was not a result of antihabituation effects of cocaine.
Subject(s)
Cocaine/pharmacology , Habituation, Psychophysiologic/drug effects , Motor Activity/drug effects , Animals , Conditioning, Psychological/drug effects , Dopamine Uptake Inhibitors/pharmacology , Male , Rats , Rats, Sprague-DawleyABSTRACT
Aged (23 months) and young (3 months) rats were trained on an operant Matching-To-Position (MTP) task that had either (a) specific outcomes (reinforcers) correlated (differential groups), or (b) outcomes uncorrelated (nondifferential groups) for each correct sample-choice sequence. The traditional version of MTP uses a common outcome and is thought to assess spatial working memory. Aged rats are impaired on the traditional version of MTP. However, aged animals trained with the Differential Outcomes Procedure (DOP) did not display the typical age-related decline in spatial working memory. Differences in choice accuracy between old and young rats reached significance only if the subjects were trained with a nondifferential outcomes procedure (NOP)-similar to when a common outcome is used. These data demonstrate that employing behavioral procedures to tap intact cognitive functions is an effective means of enhancing spatial working memory in normal as well as aged subjects.
