Faculty Bibliography

Electrical stimulation frequency thresholds for lateral hypothalamic (LH) self-stimulation were monitored throughout a 3 week period of food restriction and a subsequent 3 week period of re-feeding. Rats with electrodes placed in the perifornical LH were sensitive to this dietary manipulation as evidenced by a high positive correlation between body weight and self-stimulation threshold. Rats with electrodes in the zona incerta/subincertal region or ventral hypothalamus displayed little or no change in threshold. Lateral ventricular injection of naltrexone (200.0 nM) reversed the decline in threshold that was otherwise present during food restriction in rats with perifornical placements. Naltrexone had no effect on thresholds of rats with placements outside the perifornical region. These findings suggest that food restriction and weight loss activate an opioid mechanism that facilitates perifornical LH self-stimulation. The documented association of perifornical LH with the phenomenon of stimulation-induced feeding, and the reciprocal connections between this region and gustatory structures, supports the hypothesis that facilitation of self-stimulation by food restriction is related to the natural phenomenon of positive alliesthesia (i.e. the hunger-dependency of food reward)

The role of central kappa opioid receptors in the regulation of feeding and reward was evaluated using electrical brain stimulation paradigms in combination with the selective kappa antagonist, norbinaltorphimine (nor-BNI). Lateral ventricular injection of 10.0 and 50.0 nmol doses of nor-BNI increased the lateral hypothalamic stimulation frequency threshold for eliciting feeding behavior but had no effect on threshold for self-stimulation in the absence of food. This result is identical to those previously reported for naloxone and antibodies to dynorphin A and suggests that opioid activity is associated with feeding behavior rather than the eliciting brain stimulation. A further similarity between naloxone, dynorphin antiserum, and nor-BNI is their preferential effect on feeding threshold values obtained later, rather than initially, in a post-injection test session. This pattern of threshold elevation is shown to differ from that of the appetite suppressants, amphetamine and phenylpropanolamine, which elevate threshold uniformly throughout a post-injection test. The signature pattern of threshold elevation produced by opioid antagonism is consistent with the hypothesis that opioid activity is involved in the maintenance rather than the initiation of feeding. Specifically, it is hypothesized that a dynorphin A/kappa receptor mechanism is triggered by food taste and sustains feeding behavior by facilitating incentive reward

The pontine parabrachial nucleus (PBN) contains gustatory relay neurons and a high concentration of opioid receptors. To investigate the involvement of PBN opioid activity in feeding behavior, antagonists were infused into the PBN bilaterally and effects on stimulation-induced feeding were determined. Naloxone, a mu-preferring antagonist, increased the lateral hypothalamic stimulation threshold for eliciting feeding behavior while nor-binaltorphimine, a kappa-selective antagonist, did not. Neither antagonist increased threshold when infused into dorsal pontine sites outside of the PBN or the fourth ventricle. In as much as PBN contains mu and kappa but no detectable delta receptors, the present results suggest that mu opioid activity within the PBN is involved in the mediation of feeding behavior