The present study investigated the effect of a potential pharmacotherapy, olanzapine (OLZ), in its ability to inhibit relapse in an animal model: the extinction/reinstatement model. Seventy-five male Sprague-Dawley rats (276--300 g) were implanted with permanent, indwelling jugular vein catheters and trained to self-administer methamphetamine (MA) (0.12 mg/kg/injection) in a standard operant self-administration chamber in one hour sessions. Once stable responding was achieved (<20% variance across three days), an extinction procedure was employed whereby lever presses no longer resulted in the delivery of drug, but only saline vehicle. Once extinguished (<10% normal responding), rats were randomly assigned to one of three reinstatement cue conditions: light-cued, drug-cued, or light and drug-cued. In the drug cued reinstatement condition, rats received one of two priming doses of MA (0.5, 1.0 mg/kg, i.p.) 15 minutes prior to the self-administration session. In the non-drug cued condition, a stimulus light (previously extinguished) served as the reinstatement cue. Further, within each condition, animals were randomly assigned to a pretreatment conditions of either saline or one of two doses of OLZ (1.0, 2.0 mg/kg, s.c., 1 hour pre). Lever presses resulted in saline infusions during the reinstatement sessions. Results indicate that both drug (MA) and non-drug (light) cues were sufficient to reinstate drug seeking (lever presses). Although olanzapine appears to reduce drug and non-drug cued reinstatement, these effects were not significant within groups. However, when collapsed across groups, OLZ significantly reduces MA self-administration. |