Effects of lorcaserin on reinstatement of responding previously maintained by cocaine or remifentanil in rhesus monkeys

Drug abuse remains a serious public health issue, underscoring the need for additional treatment options. Agonists at serotonin (5-HT)_2C receptors, particularly lorcaserin, are being considered as pharmacotherapies for abuse of a variety of drugs, including cocaine and opioids. The current study compared the capacity of lorcaserin to attenuate reinstatement of extinguished responding previously maintained by either cocaine or an opioid; this type of procedure is thought to model relapse, an important aspect of drug abuse. Six rhesus monkeys responded under a fixed-ratio schedule for cocaine (0.032 mg/kg/infusion) or remifentanil (0.00032 mg/kg/infusion). Reinstatement of extinguished responding was examined following administration of noncontingent infusions of cocaine (0.32 mg/kg) or heroin (0.0032-0.1 mg/kg) combined with response-contingent presentations of the drug-associated stimuli, or heroin alone without presentation of drug-associated stimuli. When combined with drug-associated stimuli, cocaine and heroin increased extinguished responding. On average, monkeys emitted fewer reinstated responses following 0.32 mg/kg cocaine, compared with the number of responses emitted when cocaine was available for self-administration or when extinguished responding was reinstated by 0.032 mg/kg heroin. When drug-associated stimuli were not presented, heroin did not increase responding. Lorcaserin dose dependently attenuated reinstated responding, and its potency was similar regardless of whether cocaine or heroin was given before reinstatement sessions. The generality of this effect of lorcaserin across pharmacological classes of abused drugs might make it particularly useful for reducing relapse-related behaviors in polydrug abusers.