A concurrently available negative reinforcer robustly decreases cocaine self-administration in male and female rats

Continued drug-taking despite adverse consequences is hypothesized to be an insidious behavioral hallmark of drug addiction. Although most preclinical research has focused on drug self-administration in the presence of positive punishment, another source of potential adverse consequences is behavioral allocation away from negative reinforcers (i.e., escape/avoid electric shock) and towards drug reinforcers. The goals of the present study were to establish a discrete-trial cocaine-vs-negative reinforcer choice procedure in male and female rats and determine sensitivity of choice behavior to environmental and pharmacological manipulations. Rats could make up to nine discrete choices between an intravenous cocaine infusion (0.32 - 1.8 mg/kg/inf) under a fixed-ratio (FR) 3 schedule and a negative reinforcer (escape or avoidance of electric shock, 0.1 - 0.7 mA) under an FR1 schedule. The negative reinforcer was consistently chosen over all cocaine doses. Lowering shock magnitude decreased negative reinforcer trials, increased omitted trials, and failed to promote behavioral reallocation towards cocaine. Increasing the negative reinforcement response requirement between sessions only increased omitted trials. Introduction of 12-hr extended access cocaine self-administration sessions across two weeks resulted in high daily cocaine intakes but failed to significantly increase cocaine choice. Acute diazepam pretreatment also did not impact choice behavior up to doses that produced behavioral depression. Overall, the lack of behavioral allocation between cocaine infusions and a negative reinforcer suggests these two reinforcers may be economic independents. Additionally, the failure of extended cocaine access to increase cocaine choice highlights the importance of alternative reinforcers and environmental context in preclinical models of drug addiction.