Chronic morphine impairs interoceptive control of avoidance: Implications for dysregulated drug intake

Interoceptive drug states have been increasingly recognized as important cues that may help regulate intake by disambiguating postintake outcomes. While drug states signaling rewarding or reinforcing effects may occasion drug-taking and drug-seeking, states signaling aversive effects may be critical for terminating a drug-taking episode. Given that drug intake often becomes dysregulated with extensive exposure, the present study investigated whether chronic drug exposure impairs the function of interoceptive drug states to occasion avoidance. Male Sprague Dawley rats were trained in a discriminated taste avoidance procedure in which morphine (10 mg/kg, intraperitoneally) signaled that a saccharin solution would be followed by the illness-inducing agent lithium chloride, while the drug vehicle signaled that saccharin would not be followed by lithium chloride. Rats were then exposed to chronic morphine (CM) or chronic vehicle for 20 days. Morphine-induced stimulus control was tested at three doses (0, 5, and 10 mg/kg) following chronic exposure and a 3-week morphine-free period (dissipation of tolerance). Forty-five of the 49 rats acquired the discrimination, avoiding saccharin when it was preceded by morphine and consuming saccharin when it was preceded by saline. Chronic vehicle-exposed rats displayed dose-dependent avoidance on a subsequent test, while CM-exposed rats displayed no avoidance at any dose. Following a 30-day washout during which morphine was no longer administered, subjects in group CM injected with 10 mg/kg morphine avoided saccharin, displaying a partial recovery of discriminative control. These findings provide a baseline for the attenuating effects of chronic drug exposure on the drug's interoceptive control of avoidance. Further, by demonstrating that interoceptive control recovers after abstinence, the results suggest that tolerance may contribute to such impairment. (PsycInfo Database Record (c) 2025 APA, all rights reserved).