A main problem in the treatment of human cocaine addiction is high rates of relapse to drug use after periods of forced or self-imposed abstinence. This relapse is often induced by acute exposure to drug-associated cues. Researchers have extensively studied the ability of drug cues to provoke 'relapse' in laboratory animals, using a reinstatement model in which resumption of drug seeking is assessed after extinction of drug-reinforced responding; in this model, there are no adverse consequences of drug-seeking behavior. However, in human drug users abstinence is often self-imposed, and relapse episodes likely involve making a choice between the desire for the drug and the negative consequences of pursuing it (a conflict situation). To this end, we have begun to develop a 'conflict model of cue-induced relapse' in rats that better mimics the human condition described above. In initial studies, we trained rats to lever- press for cocaine for 2-3 h/d over 10-13 d; infusions were paired with a 20-sec discrete light cue. We then introduced an 'electric barrier' by electrifying the floor area near the levers. Responding decreased over 4-9 days with increasing shock intensities, until the rats did not approach the levers for 3 consecutive days. Subsequently, we assessed the effect of non- contingent light cue presentations on resumption of lever responding (relapse), while the electric barrier remained activated. We found that exposure to cocaine cues led to resumption of lever responding during the relapse tests in 14 of the 24 rats tested. In this application, we propose to further develop the conflict model of cue-induced relapse to cocaine seeking, and to explore its utility for studying cue-induced relapse to methamphetamine seeking. We hope that results from the proposed studies will encourage other preclinical investigators to adapt our model for studying mechanisms underlying cue-induced drug relapse under conditions that more closely resemble the human condition. ? ? ?
| Barnea-Ygael, Noam; Yadid, Gal; Yaka, Rami et al. (2012) Cue-induced reinstatement of cocaine seeking in the rat ""conflict model"": effect of prolonged home-cage confinement. Psychopharmacology (Berl) 219:875-83 |
