EFFECTS OF INTRATHECAL OR INTRACEREBROVENTRICULAR PRETREATMENT WITH PERTUSSIS TOXIN ON ANTINOCICEPTION INDUCED BY BETA-ENDORPHIN OR MORPHINE ADMINISTERED INTRACEREBROVENTRICULARLY IN MICE

We have previously demonstrated that beta-endorphin and morphine, when administered supraspinally, produce antinociception by activating dif ferent descending pain inhibitory systems in both rats and mice. Howev er, the signal transduction mechanisms involved in the descending pain -inhibitory systems that are activated by beta-endorphin and morphine administered intracerebroventricularly (i.c.v.) have not been characte rized. Therefore, in the present study, the effects of intrathecal (i. t.) and i.c.v. pretreatments with pertussis toxin (PTX) on antinocicep tion induced by beta-endorphin or by morphine administered i.c.v. were studied in ICR mice. Antinociception was assessed by the tail-flick a ssay and by the hotplate assay. Intrathecal pretreatment with PTX (0.5 mu g) for 6 days effectively reduced the inhibition of the tail-flick response induced by beta-endorphin (1 mu g) or by morphine (1 mu g) a dministered i.c.v. However, i.t. pretreatment with PTX was not effecti ve in reducing the inhibition of the hot-plate response induced by bet a-endorphin or by morphine administered i.c.v. Intracerebroventricular pretreatment with PTX (0.5 mu g) for 6 days effectively reduced the i nhibition of the tail-flick and hot-plate responses induced by morphin e (1 mu g), but not that induced by beta-endorphin (1 mu g), administe red i.c.v. Our results suggest that there are PTX-sensitive G proteins coupled to the spinal descending pain inhibitory systems that are act ivated by beta-endorphin and morphine administered i.c.v. At a suprasp inal level, i.c.v. morphine- but not beta-endorphin-induced antinocice ption is mediated by PTX-sensitive G proteins.