Effects of cocaine self-administration on food-reinforced responding using a discrete trial procedure in rats.

Cocaine addiction has been characterized by a shift from controlled to uncontrolled and compulsive drug use. Using novel self-administration procedures, we attempted to model this transitional phase and characterize the behavioral changes that underlie it. We chose to use food-reinforced responding across the light/dark cycle as an indicator of the degree to which cocaine was disrupting ongoing behavior as a potential measure of dysregulation. Four groups of rats (n=5-6) were given 24-h access to cocaine (1.5 mg/kg/inj) available in 2, 3, 4, or 5 discrete trials/h. All rats were given continuous access to a second lever that resulted in the delivery of a 45 mg food pellet under a fixed ratio 1 schedule. The results showed that under low access conditions (eg 2 discrete trials/h), both food- and cocaine-reinforced responding were diurnally regulated and occurred coincidentally. As access to cocaine was increased, there was a progressive disruption in the diurnal control over both food- and cocaine-maintained responding. High access conditions also produced transient decreases in the total levels of food-reinforced responding. These findings suggest that high access to cocaine under the discrete trial cocaine self-administration procedure produces a transient disruption in the diurnal control over behavior maintained by food and that the level of control (or loss of) may be a useful marker of dysregulation.