Mu‐opioid receptor knockout mice show diminished food‐anticipatory activity

We have previously suggested that during or prior to activation of anticipatory behaviour to a coming reward, µ‐opioid receptors are activated. To test this hypothesis schedule induced food‐anticipatory activity in µ‐opioid receptor knockout mice was measured using running wheels. We hypothesized that µ‐knockout mice show little food‐anticipatory activity. In wildtype mice we observed that food‐anticipatory activity increased proportional to reduced food intake levels during daily scheduled food access, and thus reflects the animal's physiological need for food. µ‐Knockout mice do not adjust their schedule induced running wheel behaviour prior to and during feeding time in the same way as wildtype mice; rather than showing more running wheel activity before than during feeding, they showed an equal amount of activity before and during feeding. As food‐anticipatory activity is dependent on the mesolimbic dopamine system and µ‐opioid receptors regulate dopaminergic activity, these data suggest a change in the dopamine system's activity in µ‐knockout mice. As we observed that µ‐knockout mice tended to show a stronger locomotor activity response than wildtype mice to the indirect dopamine agonist d ‐amphetamine, it appears that the dopaminergic system per se is intact and sensitive to activation. We found no differences in the expression of pro‐opiomelanocortin, a precursor of endogenous endorphin, in the arcuate nucleus between µ‐knockout mice and wildtype mice during restricted feeding, showing that the µ‐opioid receptor does not regulate endogenous endorphin levels. These data overall suggest a role for µ‐opioid receptors in adapting reward related behaviour to the requirements of the environment.