Impact of a high fat/sugar diet on morphine-stimulus control: implications for dysregulated drug intake.

Our recent findings showed that rats can learn to use morphine administration as an interoceptive discriminative stimulus that signals when saccharin intake will be followed by malaise. This outcome suggests that interoceptive drug-induced state cues present during a bout of drug taking could downregulate drug intake by predicting the onset of nonrewarding or aversive consequences. Accordingly, factors that impair the ability of interoceptive state cues to signal these outcomes could contribute to increased drug consumption. Previous work showed that consuming an obesity-promoting high-fat/high-sugar (HF/HS) diet impaired the ability of rats to discriminate interoceptive cues corresponding to hunger and satiety. The present research explores the possibility that prior maintenance on a HF/HS diet would also impair the ability of rats to utilize interoceptive signals produced by morphine administration. Rats raised from adolescence to adulthood on standard chow or on a HF/HS diet) were trained over seven cycles in which morphine (5 mg/kg, IP) signaled a saccharin-LiCl pairing, while saline signaled saccharin alone. Chow-fed rats acquired the discrimination within three cycles, avoiding saccharin after morphine but consuming it after saline. HF/HS rats failed to learn the discrimination, consuming saccharin at high levels regardless of the injection. Locomotor activity tests revealed that morphine suppressed movement in HF/HS rats, indicating that morphine remained behaviorally active despite impaired learning. These results suggest that drug intake regulation may be dependent on interoceptive cues, and impaired control by those cues may contribute to dysregulated drug intake.