title: The modulatory effects of mu and kappa opioid agonists on 5-HT release from hippocampal and hypothalamic slices of euthermic and hibernating ground squirrels.
abstract: To elucidate the role of opioids in regulating hibernation, the modulatory effects of different opioids on 35 mM K(+)-stimulated [3H]-5-HT release from brain slices were examined in the Richardson's ground squirrels. DAGO ([D-Ala2,N-Me-Phe4,Gly-ol5]-enkephalin), a specific mu agonist, evoked a significant dose-dependent (10(-7)-10(-5) M) inhibition of K(+)-stimulated 5-HT release from hippocampal slices of the non-hibernating squirrels. The inhibitory effect of DAGO was attenuated by either the opioid antagonist naloxone (10(-6) M) or the voltage dependent sodium channel blocker tetrodotoxin (TTX, 10(-6) M). The inhibitory effect of DAGO persisted in the hibernating squirrels; however, a ten fold higher concentration of DAGO (10(-6)-10(-5) M) was required to elicit a significant inhibition. In contrast, kappa agonist U50488 (10(-5) M) exerted a significant enhancement of K(+)-stimulated 5-HT release from hippocampal slices of the non-hibernating squirrels. This enhancement was blocked by either the specific kappa antagonist nor-binaltorphimine (10(-6) M) or TTX (10(-6) M). However, in the hibernating squirrels, the stimulatory effect of U50488 (10(-5) M) on 5-HT release was absent. DAGO and U50488 had no modulatory effects on K(+)-stimulated 5-HT release from the hypothalamic slices of either the non-hibernating or hibernating squirrels. These results demonstrate that the modulatory effects of opioids on 5-HT release are receptor-specific and state-dependent, indicating the complex nature of the roles of different opioids in regulating hibernation.
authors.affiliation: Department of Zoology, University of Alberta, Edmonton, Canada.
authors.forename: Y
authors.initials: Y
authors.lastname: Cui
authors.forename: T F
authors.initials: TF
authors.lastname: Lee
authors.forename: L I
authors.initials: LI
authors.lastname: Kramarova
authors.forename: L C
authors.initials: LC
authors.lastname: Wang
mesh_terms: D000595:Amino Acid Sequence; D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D001831:Body Temperature / Q000502:physiology*; D004723:Endorphins / Q000502:physiology; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004745:Enkephalins / Q000494:pharmacology; D005260:Female; D006605:Hibernation / Q000502:physiology*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D008297:Male; D008969:Molecular Sequence Data; D009270:Naloxone / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D017473:Receptors, Opioid, kappa / Q000502:physiology*; D017450:Receptors, Opioid, mu / Q000502:physiology*; D012589:Sciuridae / Q000502:physiology*; D012701:Serotonin / Q000378:metabolism* / Q000502:physiology; D013268:Stimulation, Chemical; D013779:Tetrodotoxin / Q000494:pharmacology
chemical_list: D000700:Analgesics; D004723:Endorphins; D004745:Enkephalins; D009294:Narcotics; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D012701:Serotonin; D009270:Naloxone; D013779:Tetrodotoxin; D011188:Potassium