THE INFLUENCE OF BAY K-8644 TREATMENT ON (+ -)-EPIBATIDINE-INDUCED ANALGESIA/

The purpose of this investigation was to determine if analogous to (-) -nicotine's analgesic effect, the analgesic effect of the recently cha racterized potent nicotinic acetylcholine receptor (nAChR) agonist (+/ -)-epibatidine was altered in response to treatment with the calcium c hannel agonist (+/-)-Bay K 8644. In addition, the effects of the enant iomers, (+)-Bay K 8644, reported to be a calcium channel antagonist, a nd (-)-Bay K 8644, reported to be a calcium channel agonist were exami ned. (+/-)-Bay K 8644 (2.8 mu mol/kg; i.p.) produced a large analgesic response in mice in the hot-plate paradigm that rapidly dissipated by 30 min after treatment. This analgesic effect of (+/-)-Bay K 8644 was not prevented by pre-treatment with the nicotinic antagonist mecamyla mine (5 mu mol/kg; i.p.). Treatment with non-analgesic doses of the ca lcium channel agonists (+/-)- and (-)-Bay K 8644 (1.4 mu mol/kg; i.p.) significantly potentiated the analgesic effect of (+/-)-epibatidine ( 0.05 mu mol/kg; i.p.). Potentiation of (+/-)-epibatidine's analgesic e ffect occurred when the agonists were administered prior to (+/-)-epib atidine or after (+/-)-epibatidine as long as analgesia testing was co nducted 15 to 30 min after Bay K 8644 treatment. Pre-treatment with th e calcium channel antagonist (+)-Bay K 8644 was found to attenuate (+/ -)-epibatidine-induced analgesia. When given after (+/-)-epibatidine, (+)-Bay K 8644 had no effect on (+/-)-epibatidine's analgesic effect. These data provide additional in vivo evidence that altering calcium d ynamics can modulate neuronal nAChR function.