Norbinaltorphimine blocks the feeding but not the reinforcing effect of lateral hypothalamic electrical stimulation.

Abstract

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.