Activating mu-opioid receptors in the lateral parabrachial nucleus increases c-Fos expression in forebrain areas associated with caloric regulation, reward and cognition.
The pontine parabrachial nucleus (PBN) has been implicated in the modulation of ingestion and contains high levels of mu-opioid receptors (MOPRs). In previous work, stimulating MOPRs by infusing the highly selective MOPR agonist [d-Ala2, N-Me-Phe4, Gly5-ol]enkephalin (DAMGO) into the lateral parabrachial region (LPBN) increased food intake. The highly selective MOPR antagonist d-Phe-Cys-Trp-Arg-Thr-Pen-Thr-NH2 (CTAP) prevented the hyperphagic action of DAMGO. The present experiments aimed to analyze both the pattern of neural activation and the underlying cellular processes associated with MOPR activation in the LPBN. Male Sprague-Dawley rats received a unilateral microinfusion of a nearly maximal hyperphagic dose of DAMGO into the LPBN. We then determined the level of c-Fos immunoreactivity in regions throughout the brain. MOPR activation in the LPBN increased c-Fos in the LPBN and in the nucleus accumbens, hypothalamic arcuate nucleus, paraventricular nucleus of the thalamus and hippocampus. Pretreatment with CTAP prevented the increase in c-Fos translation in each of these areas. CTAP also prevented the coupling of MOPRs to their G-proteins which was measured by [(35)S] guanosine 5'-O-[gamma-thio]triphosphate ([(35)S]GTPgammaS) autoradiography. Together, these data strongly suggest that increasing the coupling of MOPRs to their G-proteins in the LPBN disinhibits parabrachial neurons which subsequently leads to excitation of neurons in regions associated with caloric regulation, ingestive reward and cognitive processes in feeding.
Department of Pharmacology and Physiology, Drexel University College of Medicine, 245 N 15th Street, 19 Floor MS 400, Philadelphia, PA 19102, USA.
M
M
Denbleyker
D M
DM
Nicklous
P J
PJ
Wagner
H G
HG
Ward
K J
KJ
Simansky
D000818:Animals; D001345:Autoradiography; D003071:Cognition / Q000502:physiology*; D002149:Energy Intake / Q000502:physiology*; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000494:pharmacology; D005247:Feeding Behavior / Q000502:physiology; D019204:GTP-Binding Proteins / Q000378:metabolism; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D007150:Immunohistochemistry; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D009842:Oligopeptides / Q000494:pharmacology; D011149:Pons / Q000187:drug effects* / Q000378:metabolism; D016548:Prosencephalon / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis*; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D017450:Receptors, Opioid, mu / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000378:metabolism; D012201:Reward
D009842:Oligopeptides; D016760:Proto-Oncogene Proteins c-fos; D017450:Receptors, Opioid, mu; C543507:phenylalanyl-cysteinyl-tryptophyl-arginyl-threonyl-penicillamine-threoninamide; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D019204:GTP-Binding Proteins