INDIVIDUAL-DIFFERENCES IN THE PSYCHOMOTOR EFFECTS OF MORPHINE ARE PREDICTED BY REACTIVITY TO NOVELTY AND INFLUENCED BY CORTICOSTERONE SECRETION

Clinical observations show that individual vulnerability to the reinforcing properties of drugs plays an important part in the subsequent development of addiction. In animals, individual vulnerability to psychostimulants has been found to be predicted by their locomotor response to novelty as well as their corticosterone response. Rats with a high locomotor response to novelty (High. Responders or HR) relative to Low Responders (LR), show a higher sensitivity to both the psychomotor and reinforcing effects of psychostimulants and a longer lasting corticosterone secretion in response to stress. In this study, we addressed two main questions. First, does the locomotor response to novelty also predict the psychomotor effects of morphine? Second, do differences in corticosterone secretion underlie individual differences in the stimulant effects of morphine? We compared the locomotor response to morphine (2 mg/kg s.c.) in: (i) HR and LR rats with an intact hypothalamo-pituitary-adrenal (HPA) axis; (ii) HR and LR rats in which stress-induced corticosterone secretion was suppressed by adrenalectomy but basal levels of corticosterone were maintained by implantation of subcutaneous corticosterone pellets. In animals with an intact HPA axis, HR rats showed a higher locomotor response than did LRs to morphine. In animals in which corticosterone secretion was suppressed, the enhanced locomotor response of the HRs to morphine fell to that observed in the LRs. In conclusion our data show that, (1) individual reactivity to novelty can predict individual vulnerability to the psychomotor effects of opioids, and (2) stress-induced corticosterone secretion may play a role in determining individual differences in sensitivity to these drugs. These results are comparable to those observed with psychostimulants, and suggest that a common biological mechanism underlies individual vulnerability to the effects of both classes of drugs.