Conditioned aversive responses produced by delayed, but not immediate, exposure to cocaine and morphine in male Sprague-Dawley rats

Abstract

Rationale: To determine the conditions under which tastes paired with delayed access to experimenter-delivered cocaine and morphine elicit a conditionally aversive affective state.

Objectives and methods: The potential of saccharin paired with immediate access to cocaine (5, 10, 20 mg/kg, sc and ip) and delayed (30 and 10 min) access to cocaine (20 mg/kg, sc and ip) and morphine (10 mg/kg, sc) to elicit a pattern of aversive responding in the taste reactivity test (Grill and Norgren 1978a) was evaluated. Cocaine-induced aversions were compared with those produced by a moderate dose of LiCl (50 mg/kg). Finally, as an independent measure of cocaine withdrawal, the potential of exposure to saccharin paired with delayed access to cocaine to produce anxiogenic-like responding in the Light-Dark Emersion test was evaluated.

Results: Immediate access to cocaine did not produce conditioned aversion at any dose. Delayed (30 or 10 min) access to sc cocaine (20 mg/kg) produced robust conditioned aversion and delayed access to ip cocaine (20 mg/kg; 30 min) and to sc morphine (10 mg/kg; 10 min) produced weaker conditioned aversion. Yawning emerged as a potential withdrawal response in rats conditioned with delayed (30 min) access to 20 mg/kg, sc, cocaine. Contextual cues did not produce conditioned aversion when paired with delayed access to sc cocaine (20 mg/kg). Finally, exposure to saccharin paired with delayed access to cocaine produced anxiogenic-like responding in the Light-Dark Emersion test.

Conclusion: Our results support the contention that a conditioned aversive state develops when a taste cue comes to predict the delayed availability of drugs of abuse.

Keywords: Aversion; Cocaine; LiCl; Morphine; Negative affect; Rat; Taste reactivity; Withdrawal.