Development of tolerance to effects of morphine on cardiac sympathetic response

1. In isolated guinea-pig atria, morphine potentiated the response to sympathetic stimulation in a naloxone-insensitive, but calcium-sensitive way. The potentiating effect of morphine disappeared in the presence of desmethylimipramine; moreover morphine enhanced the dose-effect curve for exogenous noradrenaline. 2. Morphine was ineffective in guinea-pig atria obtained from animals implanted with morphine pellets for 4 days; on the other hand DADLE and dynorphin-(1-13) maintained their usual inhibitory effect on cardiac sympathetic response in the same kind of preparation. 3. In atria obtained from morphine-tolerant animals and maintained in vitro in the presence of morphine, removal of morphine from the bathing solution caused a new potentiating effect.