Regulation of feeding by multiple opioid receptors in cingulate cortex; follow-up to an in vivo autoradiographic study.

A previous in vivo autoradiographic study demonstrated reduced 3H-diprenorphine binding in anterior cingulate cortex of rats that were injected (i.v.) with the radiolabeled opiate during lateral hypothalamic stimulation-induced feeding (SIF). This suggests that an opioid peptide is released in cingulate cortex during feeding and excludes binding of the tracer. The aim of the present study was to determine whether opioid activity in cingulate cortex contributes to the expression of SIF. Agonists and antagonists for multiple opioid receptors were microinjected into cingulate cortex and effects on stimulation frequency threshold for SIF were determined. Although the universal opioid antagonist naloxone (20.0 micrograms) increased threshold, high doses of selective antagonists for mu, delta, and kappa receptors--D-Tic-CTAP, natrindole and norbinaltorphimine, respectively--had no effect. The unique efficacy of naloxone may be due to this lipophilic compound's rapid diffusion throughout an extensive volume of anterior cingulate tissue. While high doses of the kappa agonist U50,488 and the delta agonist DPDPE had no effect, the mu agonist, DAGO (1.0 microgram), decreased the SIF threshold. Moreover, the threshold-lowering effect of DAGO was blocked by pretreatment with the irreversible mu antagonist beta-FNA. These results suggest that mu opioid activity in cingulate cortex can facilitate SIF but that under basal conditions endogenous opioid activity in this brain region makes only a small positive contribution, if any, to the expression of SIF.