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 μ 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, κ 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 κ 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.
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
- Pharmacology, Toxicology and Pharmaceutics(all)