Oxycodone self-administration and drug-primed responding in male and female squirrel monkeys: Effects of alternative...

Nondrug alternative reinforcers have long been used as a component of therapeutic interventions for the management of substance use disorder; however, the conditions under which alternative reinforcers are most effective are not well characterized. This study evaluated the impact of varying the magnitude of an alternative reinforcer on oxycodone self-administration and drug-primed responding in male and female squirrel monkeys. Subjects (n = 4/sex) were trained under concurrent second-order schedules of reinforcement for intravenous oxycodone (0.001-0.1 mg/kg per injection) on one lever and sweetened condensed milk (5%, 10%, 20%, and 30% in water) on another. Oxycodone-primed responding was evaluated by administering 0.32 mg/kg of oxycodone prior to sessions in which saline was available on the drug-paired lever. During oxycodone self-administration sessions, milk availability decreased oxycodone self-administration and preference in a concentration-dependent manner; low milk concentrations were more effective at decreasing oxycodone's reinforcing potency in males. During priming tests, milk significantly attenuated oxycodone-primed responding in both males and females; low milk concentrations were more effective at decreasing the priming effects of oxycodone in females. That alternative reinforcers differentially impacted self-administration and oxycodone-primed responding in a sex-dependent manner suggests that treatment strategies that use alternative reinforcers may be more effective in males or females depending on when they are implemented. SIGNIFICANCE STATEMENT: The use of nondrug reinforcer alternatives is a key component of many therapeutic interventions for substance use disorder. However, the variables that influence response to alternative reinforcers remain incompletely understood. This study investigated how varying the magnitude of an alternative reinforcer impacts oxycodone self-administration and drug-primed responding in male and female squirrel monkeys. Overall, the findings indicate that alternative reinforcers affect self-administration and oxycodone-primed responding differently depending on sex.