Tolerance to the reinforcing effects of cocaine.

This study tested the hypothesis that prolonged exposure to high doses of cocaine would produce tolerance to the reinforcing effects of cocaine. We determined the rate of administration of low doses of cocaine in rats and then exposed these subjects to high doses of cocaine (5mg) three-times a day for 1 week. This treatment caused a 2-fold faster intake of cocaine, and the lowest dose of cocaine that would maintain self-administration was double the previous threshold dose. To our knowledge this is the first controlled demonstration of tolerance to the reinforcing effects of cocaine produced by chronic exposure to the drug, and we suggest that this tolerance may be a key marker for the development of drug dependence.