Pentobarbital antagonizes the effect of morphine on cardiac acceleration response to noxious stimulation

The effects of morphine alone and in combination with pentobarbital on the cardiac acceleration response to somatic noxious stimulation were studied in 145 rats. It was found that pentobarbital in subanesthetic doses (1-10 mg X kg-1) weakened the inhibitory effect of morphine on the cardiac acceleration response; it antagonized the effect of morphine in a dose-dependent manner. The maximal antagonism was observed with a pentobarbital dose of 10 mg X kg-1. With this dose of pentobarbital, even 200 mg X kg-1 or morphine was unable to block the cardiac acceleration response (without pentobarbital, morphine blocked the response in a dose of 10 mg X kg-1). Caffeine (10 mg X kg-1), on the contrary, strengthened the effect of morphine on the cardiac acceleration response: there was a significant (P less than 0.05) shift to the left along the dose axis in the position of morphine dose-effect curve for the cardiac acceleration response. It has been suggested that the effect of morphine on the cardiac acceleration response to noxious stimulation results primarily from activation of inhibitory control mechanisms concerned with this response; pentobarbital depresses the inhibitory control mechanisms and, therefore, weakens the effect of morphine.