THE MODULATORY EFFECTS OF MU-OPIOID AND KAPPA-OPIOID AGONISTS ON 5-HT RELEASE FROM HIPPOCAMPAL AND HYPOTHALAMIC SLICES OF EUTHERMIC AND HIBERNATING GROUND-SQUIRRELS

To elucidate the role of opioids in regulating hibernation, the modulatory effects of different opioids on 35 mM K+-stimulated [H-3]-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, K 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 K 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.