Morphine influences on classical aversive conditioned heart rate in rats.

Abstract

The present series of three experiments was concerned with the effects of morphine and the morphine antagonist naloxone on the development of a classical aversive heart rate (HR) conditioned response (CR) to a tone conditioned stimulus (CS) paired with an electric shock unconditioned stimulus (US). In the first study, separate groups of rats received preconditioning sc injections of either 0.25 mg/kg, 5 mg/kg, or 10 mg/kg of morphine. Three other groups were given 0.1 mg/kg, 5 mg/kg, or 10 mg/kg of naloxone alone. All of the morphine groups showed attenuation HR responses to the CS on preconditioning CS-alone trials. During conditioning, the 10-mg/kg morphine group showed a markedly decremented bradycardia CR and tachycardia unconditioned response (UR), whereas the 5-mg/kg morphine group showed a normal CR in combination with a decremented UR. Naloxone had no measurable effects on HR. In the second study, naloxone (1 mg/kg) given after conditioning failed to reverse the CR and UR losses produced by 10 mg/kg of morphine given prior to conditioning. Administration of 10 mg/kg of morphine produced only a minor reduction in a HR CR established in a drug-free state, but the tachycardia UR was severely reduced. The results of the third study showed that 1 mg/kg of naloxone was effective in reversing analgesia induced by 10 mg/kg of morphine, as indexed by the tail-flick test. Taken together, the results suggest that the 10-mg/kg dose of morphine interfered with the learning of a HR CR, perhaps principally by reducing the aversive or emotional consequences of the shock US. Direct cardiovascular effects of morphine seemed to interfere with the performance of the tachycardia UR, but not with the performance of the bradycardia CR.