State-dependent stimulus control: Cuing attributes of acute cocaine rebound in rats.

Abstract

Sprague-Dawley (Rattus norvegicus) rats were trained in a drug discrimination task using the state-dependent interoceptive stimulus attributes of cocaine's delayed or rebound effects (CDE) versus "normal" basal homeostasis. Rats were injected with either 32 mg/kg cocaine or equivalent volumes of saline (SAL), subcutaneously, 13 hr before the sessions. Rats demonstrated > 90% discriminative accuracy. Test sessions showed a time-dependent acute cocaine isodirectional rebound state that engendered a shift from predominantly SAL- to CDE-appropriate responding approximately 7 hr after the high training dose injection and lasted for approximately 10 hr (17 hr postinjection). The delayed or rebound state was dose dependent and engendered only a biphasic partial generalization with acute cocaine injections. There were no detectable levels of cocaine or any of its behaviorally active metabolites at the 13-hr postinjection interval. Tests conducted with various doses of lidocaine, chlordiazepoxide, N-methyl-d-aspartic acid, ketamine, and buspirone engendered SAL- or default-appropriate responding. The anxiogenic drug, pentylenetetrazole, produced partial generalization to the cocaine rebound cue.