Neuroanatomical sites mediating the central actions of beta-endorphin as mapped by changes in glucose utilization: involvement of mu opioid receptors.
Local cerebral glucose utilization, which is a correlate of neuronal activity, was measured to obtain information on the neuroanatomical sites mediating the different behaviors elicited by i.c.v. administration of the opioid peptide beta-endorphin (beta-END). The selective mu and delta opioid receptor antagonists d-Phe-Cys-Tyr-d-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP) and ICI 174,864 (N,N-diallyl-Tyr-Aib-Aib-Phe-Leu-OH), respectively, were used to characterize the opioid receptor type involved in the actions of beta-END. beta-END was found to produce profound increases in glucose utilization in limbic regions such as the lateral septal nucleus, the amygdalo-hippocampal transition area, the nucleus accumbens and the hippocampal formation. The ventral hippocampus proved the most sensitive structure, displaying increases in glucose utilization of up to 200%; changes in the dorsal part amounted up to 100%. Only moderate effects were induced by beta-END in motor areas, such as the substantia nigra, pars reticulata and the nucleus ruber. This regional pattern of changes is assumed to underlie the epileptogenic-, motivational-, mood- and possibly memory-modulating actions of beta-END. The effects of beta-END on local cerebral glucose utilization were blocked by pretreatment with the mu antagonist, CTOP, whereas the selective delta opioid antagonist ICI 174,864 was less effective. An involvement of predominantly mu opioid receptors in the central actions of beta-END is, therefore, suggested.
Ableitner
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Institute of Pharmacology, Toxicology and Pharmacy, University of Munich, Federal Republic of Germany.
Schulz
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D000818:Animals; D001345:Autoradiography; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004743:Enkephalin, Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism; D007276:Injections, Intraventricular; D008297:Male; D009292:Narcotic Antagonists / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000187:drug effects*; D017450:Receptors, Opioid, mu; D013004:Somatostatin / Q000031:analogs & derivatives / Q000494:pharmacology; D001615:beta-Endorphin / Q000494:pharmacology*
D009292:Narcotic Antagonists; D011957:Receptors, Opioid; D017450:Receptors, Opioid, mu; C049352:phenylalanyl-cyclo(cysteinyltyrosyl-tryptophyl-ornithyl-threonyl-penicillamine)threoninamide; D013004:Somatostatin; D004743:Enkephalin, Leucine; D001615:beta-Endorphin; C040643:N,N-diallyl-tyrosyl-alpha-aminoisobutyric acid-phenylalanyl-leucine; D005947:Glucose