Reversal by Narcotic Antagonist of a Narcotic Action elicited by a Conditional Stimulus

Abstract

THERE is considerable evidence to indicate that learning is important in narcotic dependence¹. However, there has been little animal research into the mechanism of the interaction between environmental stimuli and drug action which maintains dependence. In morphine-dependent rats² and monkeys³ conditional stimuli previously associated with withdrawal can elicit physiological disturbances characteristic of narcotic withdrawal. Also, during withdrawal the conditional stimuli previously associated with morphine substitution can elicit blockade of morphine withdrawal⁴. In an experiment by Roffman et al.⁴, after a number of pairings with morphine injections, a neutral stimulus (bell) elicited a blockade of withdrawal hypothermia, a task normally accomplished by morphine itself. It was then suggested that there is an overlap between the brain mechanisms sensitive to morphine action and those affected by conditional stimuli⁵. Therefore, repeated pairing of hyperthermic effects of morphine with the stimulus-induced neural activity results in the conditioning of the former to the latter. We reasoned that if the brain activity due to a conditional stimulus evokes activity of the morphine receptors, a morphine antagonist should reverse the effectiveness of that stimulus in mimicking the morphine action. To obtain evidence in favour of this hypothesis we used naloxone, a specific antagonist of morphine action⁶.