Abstract
Self-stimulation thresholds were determined in rats by means of a modification of the psychophysical method of limits. Reinforcement values were determined after the administration of d-amphetamine alone, naloxone alone, and naloxone administered concurrently with d-amphetamine. d-Amphetamine yielded dose-related decreases in the threshold (0.25–2.00 mg/kg IP), while naloxone alone (2.0–16 mg/kg IP) caused no consistent changes. For each animal, a dose of d-amphetamine that substantially lowered the threshold was then selected to be administered with varying doses of naloxone. The threshold-lowering effect of d-amphetamine was blocked by naloxone at doses as low as 2.0 or 4.0 mg/kg. This finding suggests the possible involvement of an opiate receptor in the mediation of the enhancement by d-amphetamine of brain stimulation reward.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Adam-Carrière, D., Merali, Z., Stretch, R.: Effects of morphine, naloxone, d,l-cyclazocine, and d-amphetamine on behavior controlled by a schedule of interresponse time reinforcement. Can. J. Physiol. Pharmacol. 56, 707–720 (1978)
Belluzzi, J. D., Stein, L.: Enkephalin may mediate euphoria and drive reduction reward. Nature 266, 556–558 (1977)
Biggio, G., Casu, M., Corda, M. G., DiBello, C., Gessa, G. L.: Stimulation of dopamine synthesis in caudate nucleus by intrastriatal enkephalins and antagonism by naloxone. Science 200, 552–554 (1978)
Cassens, G. P., Mills, A. W.: Lithium and amphetamine: Opposite effects on threshold of intracranial reinforcement. Psychopharmacologia 30, 283–290 (1973)
Dettmar, P. W., Cowans, A., Walter, D. S.: Naloxone antagonizes behavioral effects of d-amphetamine in mice and rats. Neuropharmacology 17, 1041–1044 (1978)
Esposito, R., Kornetsky, C.: Morphine lowering of self-stimulation thresholds: Lack of tolerance with long-term administration. Science 195, 189–191 (1977)
Haber, S., Hatsukami, T., Berger, P. A., Barchas, J. D., Akil, H.: Naloxone blocks amphetamine-induced rearing: Potential interaction between catecholamines and endorphins. Prog. Neuropsychopharmacology 2, 425–430 (1978)
Holtzman, S. G.: Behavioral effects of separate and combined administration of naloxone and d-amphetamine. J. Pharmacol. Exp. Ther. 189, 51–60 (1974)
Holtzman, S. G.: Comparison of the effects of morphine, pentazocine, cyclazocine, and amphetamine on intracranial self-stimulation in the rat. Psychopharmacologia 46, 223–227 (1976)
Jacobowitz, D. M., Silver, M. A., Soden, W. G.: Mapping of leuenkephalin-containing axons and cell bodies of the rat forebrain. In: Endorphins in mental health research, E. Usdin, W. E. Bunney, Jr., N. S. Kline, eds., pp. 62–73 New York: Oxford University Press 1979
Koob, G. F., Winger, G. D., Meyerhoff, J. L., Annau, Z.: Effects of d-amphetamine on concurrent self-stimulation of forebrain and brain stem loci. Brain Res. 137, 109–126 (1977)
Kornetsky, C., Esposito, R. U., McLean, S., Jacobson, J. O.: Intracranial self-stimulation thresholds: A model for the hedonic effects of drugs of abuse. Arch. Gen. Psychiatry 36, 289–292 (1979)
Lorens, S. A., Sainati, S. M.: Naloxone blocks the excitatory effect of ethanol and chlordiazepoxide on lateral hypothalamic self-stimulation behavior. Life Sci. 23, 1359–1364 (1978)
Phillips, A. G., Fibiger, H. C.: The role of dopamine in maintaining intracranial self-stimulation in the ventral tegmentum, nucleus accumbens, and medial prefrontal cortex. Can. J. Psychol. 32, 58–66 (1978)
Pollard, H., Llorens-Cortes, C., Schwartz, J. C.: Enkephalin receptors on dopaminergic neurones in rat striatum. Nature 268, 745–747 (1977a)
Pollard, H., Llorens, C., Bonnet, J. J., Costentin, J., Schwartz, J. C.: Opiate receptors on mesolimbic dopaminergic neurons. Neurosci. Letters 7, 295–299 (1977b)
Schaefer, G. J., Holtzman, S. G.: Free-operant and autotitration brain self-stimulation procedures in the rat: A comparison of drug effects. Pharmacol. Biochem. Behav. 10, 127–135 (1979)
Schwartz, J. C., Pollard, H., Llorens, C., Malfroy, B., Gros, C., Pradelles, P., Dray, F.: Endorphins and endorphin receptors in striatum: Relationships with dopaminergic neurons. In: Advances in biochemical pharmacology, vol. 18, E. Costa, M. Trabucchi, eds., pp. 245–264. New York: Raven 1978
Spencer, J., Revzin, A.: Amphetamine, chlorpromazine, and clonidine effects on self-stimulation in caudate or hypothalamus of the squirrel monkey. Pharmacol. Biochem. Behav. 5, 149–156 (1976)
Stein, L.: Effects and interactions of imipramine, chlorpromazine, reserpine, and amphetamine on self-stimulation: Possible neurophysiological basis of depression. In: Recent advances in biological psychiatry, R. Heath, ed., pp. 288–309. New York: Plenum 1962
Stein, L.: Self-stimulation of the brain and the central stimulant action of amphetamine. Fed. Proc. 23, 836–850 (1964)
Stein, L., Belluzzi, J. D.: Brain endorphins and the sense of well-being: A psychobiological hypothesis. In: Advances in biochemical pharmacology, vol. 18, E. Costa, M. Trabucchi, eds., pp. 299–311. New York: Raven 1978
Uhl, G., Kuhar, M. J., Goodman, R. R., Snyder, S. H.: Histochemical localization of the enkephalins. In: Endorphins in mental health research, E. Usdin, W. E. Bunney, Jr., N. S. Kline, eds., pp. 74–83. New York: Oxford University Press 1979
van der Kooy, D., LePiane, F. G., Phillips, A. G.: Apparent independence of opiate reinforcement and electrical self-stimulation systems in rat brain. Life Sci 20, 981–986 (1977)
Wauquier, A., Niemegeers, C. J. E., Lal, H.: Differential antagonism by naloxone of inhibitory effects of haloperidol and morphine on brain self-stimulation. Psychopharmacologia 37, 303–310 (1974)
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Esposito, R.U., Perry, W. & Kornetsky, C. Effects of d-amphetamine and naloxone on brain stimulation reward. Psychopharmacology 69, 187–191 (1980). https://doi.org/10.1007/BF00427648
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00427648