Skip to main content
Log in

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

Psychopharmacology Aims and scope Submit manuscript

Abstract

The effect of morphine (3.75, 7.5, and 15.0 mg/kg. s.c.) on medial frontal cortex (MF) and hypothalamic self-stimulation (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 hypothalamic 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. It 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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Adams, W. J., Lorens, S. A., Mitchell, C. L.: Morphine enhances lateral hypothalamic self-stimulation in the rat. Proc. Soc. exp. Biol. (N.Y.) 140, 770–771 (1972)

    Google Scholar 

  • Carey, R. J., Goodall, E., Lorens, S. A.: Differential effects of amphetamine and food deprivation on self-stimulation of the lateral hypothalamus and medial frontal cortex. J. comp. physiol. Psychol. 88, 224–230 (1975)

    Google Scholar 

  • De Groot, J.: The rat forebrain in stereotaxic coordinates. Trans. roy. Neth. Acad. Sci. 52, 1–40 (1959)

    Google Scholar 

  • Glick, S. D., Rapaport, G.: Tolerance to the facilitatory effect of morphine on self-stimulation of the medial forebrain bundle in rats. Res. Commun. Chem. Path. Pharmacol. 9, 647–652 (1974)

    Google Scholar 

  • Hiller, J. M., Pearson, J., Simon, E. J.: Distribution of stereo-specific binding of the potent narcotic analgesic etorphine in the human brain: Predominance in the limbic system. Res. Commun. Chem. Path. Pharmacol. 6, 1052–1062 (1973)

    Google Scholar 

  • Koob, G. F., Spector, N. H., Meyerhoff, J. L.: Effects of heroin on lever pressing for intracranial self-stimulation, food and water in the rat. Psychopharmacologia (Berl.) 42, 231–234 (1975)

    Google Scholar 

  • Kuhar, M. J., Pert, C. B., Snyder, S. H.: Regional distribution of opiate receptor binding in monkey and human brain. Nature (Lond.) 245, 447–450 (1973)

    Google Scholar 

  • Leonard, C. M.: The prefrontal cortex of the rat. I. Cortical projection of the mediodorsal nucleus. II. Efferent connections. Brain Res. 12, 321–343 (1969)

    Google Scholar 

  • Lorens, S. A.: Effect of lesions in the central nervous system on lateral hypothalamic self-stimulation in the rat. J. comp. physiol. Psychol. 62, 256–262 (1966)

    Google Scholar 

  • Lorens, S. A.: Cingulate self-stimulation in the rat: Influence of repeated morphine administration. Proc. 80th Annual Convention Amer. Psychol. Ass. 7, 835–836 (1972)

    Google Scholar 

  • Lorens, S. A., Mitchell, C. L.: Influence of morphine on lateral hypothalamic self-stimulation in the rat. Psychopharmacologia (Berl.) 32, 271–277 (1973)

    Google Scholar 

  • Lorens, S. A., Vale, H.: Dissociation of the analgesic and rewarding effects of intracranial stimulation (Abstract). Acta physiol. scand. 197 (Suppl. 396) 80 (1973)

    Google Scholar 

  • Olds, J., Travis, R. P.: Effects of chlorpromazine, meprobamate, pentobarbital and morphine on self-stimulation. J. Pharmacol. exp. Ther. 128, 397–404 (1960)

    Google Scholar 

  • Rolls, E. T.: The neural basis of brain stimulation reward. Progr. Neurobiol. 3, 71–160 (1974)

    Google Scholar 

  • Routtenberg, A.: Intracranial self-stimulation pathways as substrate for stimulus-response integration. In: Efferent organization and the integration of behavior, J. D. Maser, ed., pp. 263–318. New York: Academic Press 1973

    Google Scholar 

  • Wauquier, A., Niemegeers, C. J. E., Lal, H.: Differential antagonism by naloxone of inhibitory effects of haloperidol and morphine on brain self-stimulation. Psychopharmacologia (Berl.) 37, 303–310 (1974)

    Google Scholar 

  • Way, E. L.: Distribution and metabolism of morphine and its surrogates. Res. Publ. Ass. nerv. ment. Dis. 46, 13–31 (1966)

    Google Scholar 

  • Way, E. L., Adler, T. K.: The pharmacologic implications of the fate of morphine and its surrogates. Pharmacol. Rev. 12, 383–446 (1960)

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lorens, S.A. Comparison of the effects of morphine on hypothalamic and medial frontal cortex self-stimulation in the rat. Psychopharmacology 48, 217–224 (1976). https://doi.org/10.1007/BF00423264

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00423264

Key words

Navigation