Characterization of the distribution of the cocaine priming threshold and the effect of SCH23390.

The cocaine-induced reinstatement (priming) of cocaine self-administration occurs when the cumulative concentration of cocaine reaches a threshold level that we have previously termed the cocaine priming threshold. The present studies used a modified procedure to measure the cocaine priming threshold over 4-8-month periods in individual rats. The values for the priming threshold varied between days but there was no evidence of a systematic change in the priming threshold over time, indicating that neither tolerance nor sensitization occurred. The frequency distribution of the priming threshold was significantly different from a normal distribution but was not significantly different from a log-normal distribution. Therefore, the geometric mean with its associated variance estimates, but not the arithmetic mean, appropriately describe the distribution of the cocaine priming threshold. The estimate of the geometric mean value of the priming threshold for this group of Sprague-Dawley rats was 284 (CI(95): 234-344) microg/kg of cocaine. The log-normal distribution of equieffective doses of cocaine is typical of agonist-induced pharmacological responses. In the presence of the D(1) dopamine receptor-selective antagonist SCH23390, the geometric means of the cocaine priming threshold were significantly increased in a dose-dependent manner, implying a role for D(1) dopamine receptors in the priming response. This technique provides a quantitative method for the measurement of antagonist-induced increases in the cocaine priming threshold.