Comparison of the effects of morphine on hypothalamic and medial frontal cortex self-stimulation in the rat.

The effect of morphine (3.75, 7.5, and 15.0 mg/kg, s.c.) on medial frontal cortex (MF) and hypothalamic self-stimllation (SS) was determined 1, 3, 5, and 7 h after injection for 5 consecutive days. Morphine suppressed or enhanced SS responding as a function of dose, time after injection, and the site stimulated. The MF SS groups were less sensitive to the toxic effects of morphine, and evidenced elevated rates of responding earlier after injection than the hypothalimic animals. The dose-response relationship of the MF rats, thus, clearly differed from that of the hypothalamic rats. With repeated administration, tolerance was rapidly (3-4 days) developed to the suppressive effect while the excitatory effect appeared earlier and tended to be enhanced, peaking 1 and 3 h after injection in the MF and hypothalamic groups, respectively. These data provide additional evidence against the hypothesis that the effect of morphine on SS behavior is non-specific. If it were, the time course and degree of effects should be similar, regardless of the electrode site tested. Furthermore, an inhibitory effect was not observed in the groups receiving 3.75 mg/kg although both showed a significant increase in responding 1 and/or 3 h after injection. This observation indicates that the excitatory effect is not dependent on the depressant effect and, therefore, probably is not a rebound phenomenon. It also suggests that the toxic effects of morphine can either mask or delay the appearance of its facilitatory action on SS responding.