Abstract
Tolerance to the suppressive effects of cocaine on milk drinking by rats was studied using a contingent tolerance experimental design. Three separate groups (n=6) of rats received 8.0, 16.0, or 32.0 mg/kg cocaine daily 15 min before a 15-min period of access to sweetened condensed milk for 20 days. Three additional groups of six rats each received the same chronic doses 15 min after access to milk. Milk, water, and food intake as well as body weight were measured daily. Tolerance effects were assessed by comparing initial acute dose-effect determinations with a probe dose-effect redetermination in which all rats again received doses of cocaine pre-session after having experienced the differential pre- or post-session chronic treatment. Behavioral tolerance on the milk intake measure was observed for the 8.0 mg/kg and 16.0 mg/kg doses, but not for the 32.0 mg/kg chronic treatment, even though the latter group exhibited evidence of tolerance in the water intake measure. Chronic treatment with 8.0 and 16.0 mg/kg produced different outcomes in that chronic exposure to 16.0 mg/kg in the presence of milk resulted in generalization of tolerance to both a lower (8.0 mg/kg) and a higher dose (32.0 mg/kg), but the group receiving 8.0 mg/kg did not exhibit generalization of tolerance to higher doses. Modest sensitization effects were observed in the rats treated post-session with either 8.0 or 16.0 mg/kg. Rats receiving 32.0 mg/kg pre-milk exhibited a dramatic lowering of food intake and concomitant loss in body weight compared to the same dose given after the milk access period, suggesting that pairing cocaine with a highly palatable substance may enhance its toxic effects. The observed behavioral tolerance effects were discussed in terms of (1) the reinforcement loss hypothesis, (2) the channeling hypothesis developed in the context of behavioral tolerance to amphetamine, and (3) the concept of dose-specific tolerance.
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Bowen, S.E., Fowler, S.C. & Kallman, M.J. Effects of variation in chronic dose of cocaine on contingent tolerance as assessed in a milk-drinking task. Psychopharmacology 113, 67–75 (1993). https://doi.org/10.1007/BF02244336
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DOI: https://doi.org/10.1007/BF02244336