Interoceptive sensations elicited by drugs of abuse can form associations with surrounding stimuli in a manner similar to externally perceived (i.e., exteroceptive) cues. A wide range of interoceptive stimuli have been established to guide behaviour in male rats. Here we extend that research to an opioid agonist stimulus, in both males and females. We predicted that when paired with an appetitive outcome, morphine could imbue that drug state with increasing appetitive value. Male and female rats were assigned to a feature positive (FP) or feature negative (FN) group and received daily intermixed morphine or saline sessions. For FP rats, on morphine sessions, each white noise (WN) presentation was followed by access to sucrose; on saline sessions, WN was still presented, but sucrose was withheld. FN rats learned the reverse contingency. After conditioning, rats learned to lever-press for intravenous access to morphine to assess motivation for the interoceptive stimulus. Indeed, morphine can resolve the ambiguity of reward-predictive cues in male and female rats. In males, an appetitive learning history with morphine imbued the interoceptive stimulus with conditioned reinforcing properties such that FP males showed greater morphine self-administration compared to FN counterparts. In contrast, there were no differences in morphine self-administration between FP and FN-assigned female rats. These data indicate that the valence of a learning history with an internally-perceived stimulus can alter its subsequent reinforcement value in a sex-dependent manner.

Allyson Andrade

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