EFFECTS OF INTRATHECAL INJECTION OF NIMODIPINE, OMEGA-CONOTOXIN GVIA,CALMIDAZOLIUM, AND KN-62 ON THE ANTINOCICEPTION INDUCED BY COLD-WATERSWIMMING STRESS IN THE MOUSE

The present study was designed to determine if spinal calcium channels , calmodulin, and calcium/calmodulin-dependent protein kinase II were involved in the production of antinociception induced by cold water sw imming stress (CWSS). The effects of intrathecal (i.t.) injection of n imodipine, omega-conotoxin GVIA, calmidazolium, or (S)-5-isoquinolines ulfonic acid, nolinyl-sulfonyl)methylamino]-3-oxo-3-(4-phenyl-1- piper azinyl)-propyl]phenyl ester (KN-62) on CWSS-induced antinociception we re studied in ICR mice. The antinociception was assessed by the tail-f lick test. CWSS produced inhibition of the tail-flick response. Variou s doses of nimodipine (10-40 ng), omega-conotoxin GVIA (5-40 ng), calm idazolium (10-40 ng), or KN-62 (5-40 ng) injected i.t. alone did not s how any antinociceptive effect in the tail-flick test. I.t. pretreatme nt with omega-conotoxin GVIA, calmidazolium, or KN-62 dose dependently attenuated the CWSS-induced inhibition of the tail-flick response. Ho wever, i.t. pretreatment with nimodipine did not affect the inhibition of the tail-flick response induced by CWSS. Our results suggest that spinal N-type calcium channel, calmodulin and. calcium/calmodulin-depe ndent protein kinase II may be involved in the production of antinocic eption induced by CWSS. On the other hand, CWSS-induced antinociceptio n appears not to be mediated via the spinal L-type calcium channel. (C ) 1997 Elsevier Science B.V.