The role of cholecystokinin in conditional compensatory responding and morphine tolerance in rats

As elaborated in the conditioning analysis of tolerance, cues present at th e time of drug administration become associated with the drug effect. A par ticularly salient cue that may become associated with the drug effect is th e pharmacological drug-onset cue inherent to drug administration. Drug-asso ciated cues contribute to tolerance by eliciting a conditional compensatory response that attenuates the drug effect. For example, the early drug effe ct, having been paired with the subsequent larger drug effect, may elicit t he release of antiopioid peptides that counter opioid effects, The role of a putative antiopioid peptide, cholecystokinin-8 (CCK), in the associative mechanisms of opiate tolerance was evaluated. The results of these experime nts suggest that a CCK2 receptor antagonist attenuates both the expression of opiate tolerance and the conditional compensatory response hypothesized to mediate such tolerance.