Combining the GlyT‐1 inhibitor Org 24598 with extinction training to deter relapse to cocaine self‐administration in squirrel monkeys

Extinction training has been implemented as a means to reduce the salience of cocaine‐associated cues and prevent relapse. This approach is not effective in cocaine users, due in part to cocaine‐induced dysfunction in memory systems important for extinction learning. Cognitive enhancers that increase glycine transmission might be useful for facilitating extinction learning after protracted cocaine use. The present study investigated the effects of the selective GlyT‐1 inhibitor, Org 24598. Squirrel monkeys (n=6) were trained to self‐administer cocaine under a second‐order schedule of drug delivery and cue presentation. During weekly extinction sessions in which completion of each FR unit produced the cocaine‐paired stimulus only, subjects were pretreated with Org 24598 (1.0 mg/kg; i.m.) or vehicle. Within‐session analysis during the 3 rd extinction session showed that compared to vehicle, Org 24598 significantly reduced response rates at the beginning and end of the session. Following extinction training, reacquisition of cocaine self‐administration was evaluated. Compared to vehicle, Org 24598 significantly lowered response rates up to the 5 th reacquisition session. In control tests, Org 24598 administered prior to weekly cocaine self‐administration sessions did not significantly alter responding relative to baseline. These results support the use of compounds that act via glycine transporter inhibition to promote extinction learning and subsequently deter relapse to cocaine self‐administration. Supported by NIH/NIDA grants DA024315 & RR00168