Does response-contingent access to cocaine reinstate previously extinguished cocaine-seeking behavior in C57BL/6J mice?

Abstract

Inbred strains of mice are valuable tools for determining the impact of genes and the environment on behavior. However, use of mice in intravenous (iv) cocaine self-administration (SA) extinction/reinstatement paradigms has yielded mixed results. Mice do demonstrate significant conditioned reinstatement but do not significantly reinstate previously extinguished cocaine-seeking behavior when passively primed with cocaine. We tested the hypothesis that C57BL/6J (B6) mice would reinstate previously extinguished cocaine-seeking behavior when provided with response-contingent access to conditioned cues and fixed doses of cocaine. Male B6 mice were implanted with jugular catheters and trained to lever press for cocaine infusions. Each infusion was paired with a compound stimulus (light and tone; LT). Following 14 days of SA, subjects underwent extinction training--responding resulted in no programmed consequences. After at least 5 extinction sessions, cue-primed reinstatement was tested (LT-test). For the LT-test, mice received response-contingent presentations of the LT. After the LT-test, subjects returned to extinction training. Once responding decreased to extinction criteria, cocaine priming began. During cocaine priming, mice had response-contingent access to saline, 1.05, 3.5, or 17.5 mg/kg cocaine. Response-contingent presentations of the LT significantly reinstated cocaine-seeking behavior in the mice. Response-contingent access to cocaine dose-dependently reinstated responding. Our results suggest that response-contingent access to cocaine is a robust method for modeling cocaine craving and relapse in mice.