enkephalin--ala(2)-mephe(4)-gly(5)- and Hypothermia

We have shown previously that intracerebroventricular (icv) injection of naloxone (a non-selective opioid receptor antagonist) or naloxonazine (a selective μ1-opioid receptor antagonist) at the maintenance phase of hibernation arouses Syrian hamsters from hibernation. This study was designed to clarify the role of β-endorphin (an endogenous μ-opioid receptor ligand) on regulation of body temperature (T(b)) during the maintenance phase of hibernation. The number of c-Fos-positive cells and β-endorphin-like immunoreactivity increased in the arcuate nucleus (ARC) after hibernation onset. In contrast, endomorphin-1 (an endogenous μ-opioid receptor ligand)-like immunoreactivity observed on the anterior hypothalamus decreased after hibernation onset. In addition, hibernation was interrupted by icv injection of anti-β-endorphin antiserum at the maintenance phase of hibernation. The mRNA expression level of proopiomelanocortin (a precursor of β-endorphin) on ARC did not change throughout the hibernation phase. However, the mRNA expression level of prohormone convertase-1 increased after hibernation onset. [D-Ala2,N-MePhe4,Gly-ol5] enkephalin (DAMGO, a selective μ-opioid receptor agonist) microinjection into the dorsomedial hypothalamus (DMH) elicited the most marked T(b) decrease than other sites such as the preoptic area (PO), anterior hypothalamus (AH), lateral hypothalamus (LH), ventromedial hypothalamus and posterior hypothalamus (PH). However, microinjected DAMGO into the medial septum indicated negligible changes in T(b). These results suggest that β-endorphin which synthesizes in ARC neurons regulates T(b) during the maintenance phase of hibernation by activating μ-opioid receptors in PO, AH, VMH, DMH and PH.

Topics: Analgesics, Opioid; Animals; beta-Endorphin; Body Temperature Regulation; Brain Chemistry; Cell Count; Central Nervous System; Cricetinae; Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; Hibernation; Hypothalamus; Hypothermia; Immunohistochemistry; Injections, Intraventricular; Mesocricetus; Oligopeptides; Polymerase Chain Reaction; Proprotein Convertase 1; Proto-Oncogene Proteins c-fos; Receptors, Opioid, mu

The aim of this study was to examine the role of fatty acid amide hydrolase (FAAH) on ethanol sensitivity, preference, and dependence. The deletion of FAAH gene or the inhibition of FAAH by carbamoyl-biphenyl-3-yl-cyclohexylcarbamate (URB597) (0.1 mg/kg) markedly increased the preference for ethanol. The study further reveals that URB597 specifically acts through FAAH and that cannabinoid-1 (CB(1)) receptor is critical for N-arachidonoyl ethanolamide (AEA) mediated ethanol-reinforced behavior as revealed by lack of URB597 effect in both FAAH and CB(1)-/- mice compared with vehicle-treated -/- mice. The FAAH -/- mice displayed a lower sensitivity to hypothermic and sedative effects to acute ethanol challenge. The FAAH -/- mice also exhibited a reduction in the severity of handling-induced convulsions following withdrawal from chronic ethanol exposure. The CB(1) receptor and proenkephalin gene expressions, and CB(1) receptor and mu-opioid (MO) receptor-mediated G-protein activation were found to be significantly lower in the caudate-putamen, nucleus accumbens core and shell of FAAH -/- than +/+ mice. Interestingly, the MO receptor-stimulated G-protein signaling was greater in the striatum of FAAH -/- than +/+ mice following voluntary ethanol consumption. These findings suggest that an elevation in the AEA content and its action on the limbic CB(1) receptor and MO receptor might contribute to ethanol-reinforced behavior. Treatment with drugs that decrease AEA tone might prove useful in reducing excessive ethanol consumption.

Topics: Alcohol Drinking; Amidohydrolases; Analgesics; Analgesics, Opioid; Animals; Behavior, Animal; Benzamides; Benzoxazines; Carbamates; Central Nervous System Depressants; Choice Behavior; Drug Interactions; Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; Enkephalins; Ethanol; Guanosine 5'-O-(3-Thiotriphosphate); Hypothermia; Mice; Mice, Inbred C57BL; Mice, Knockout; Morpholines; Motor Activity; Naphthalenes; Protein Binding; Protein Precursors; Receptor, Cannabinoid, CB1