Abstract
The effect of chronic administration of spiroperidol, a dopaminergic antagonist, on self-stimulation of the prefrontal cortex was investigated. When spiroperidol was administered either before or after daily self-stimulation tests for 9 days, self-stimulation rates were significantly elevated for several weeks following withdrawal of the drug. Self-stimulation of the nucleus accumbens, supracallosal bundle, and other forebrain sites was not altered, suggesting that the increased self-stimulation of the prefrontal cortex was not due to increased motor activity. Self-stimulation of the prefrontal cortex was also facilitated by chronic administration of d-amphetamine whereas self-stimulation of the supracallosal bundle was suppressed and self-stimulation of the nucleus accumbens was unchanged. The results suggest that dopamine modulates self-stimulation of the prefrontal cortex. Additionally, the effects of chronic spiroperidol on self-stimulation of this structure may model the therapeutic effects of neuroleptics in humans.
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Ahn, H. S., Makman, M. H.: Serotonin sensitive adenylate cyclase activity in monkey anterior limbic cortex: Antagonism by molindone and other antipsychotic drugs. Life Sci 23, 507–512 (1978)
Andén, N. E., Butcher, S. G., Corridi, H., Fuxe, K., Ungerstedt, U.: Receptor activity and turnover of dopamine and noradrenaline after neuroleptics. Eur. J. Pharmacol. 11, 303–314 (1970)
Anderson, J. L., Leith, N. J., Barrett, R. J.: Tolerance to amphetamine's facilitation of self-stimulation responding: Anatomical specifity, Brain Res. 145, 37–48 (1978)
Antelman, S. M., Eichler, A. J., Fisher, A. E.: Site-specific effects of chronic neuroleptic administration on brain-stimulation reward. Round table: Brain stimulation; effects on reward, learning and motivation. Paper presented at the International Congress of Physiological Sciences, Paris (1977)
Axelrod, J.: Amphetamine: Metabolism, physiological disposition and its effects on catecholamine storage. In: Amphetamines and related compounds, E. Costa, S. Garattini, eds., pp. 207–216. Proceedings of the Mario Negri Institute for Pharmacological Research, Milan, Italy. New York: Raven 1970
Baldessarini, R. J.: Chemotherapy in psychiatry. Cambridge: Harvard University Press 1977
Baudry, M., Martres, M. P., Schwartz, J. C.: Modulation in the sensitivity of noradrenergic receptors in the CNS studied by the responsiveness of the cyclic AMP system. Brain Res. 116, 111–124 (1976)
Berger, P. A.: Medical treatment of mental illness. Science 200, 974–981 (1978)
Christensen, A. V., Fjalland, B., Moller Nielsen, I.: On the supersensitivity of dopamine receptors induced by neuroleptics. Psychopharmacologia 48, 1–6 (1976)
Clay, G. A., Cho, A. K., Roberfroid, M.: Effect of diethylaminoethyl diphenylpropylacetate hydrochloride (SKF-525 A) on the norepinephrine-depleting actions of d-amphetamine. Biochem. Pharmacol. 20, 1821–1931 (1971)
DiMascio, A.: The buytrophenones: An overview of their pharmacologic and metabolic properties. In: Butyrophenones in psychiatry, A. DiMascio, R. I. Shader, eds., pp. 11–23. New York: Raven 1972
Eichler, A. J., Antelman, S. M., Fisher, A. E.: Self-stimulation: Site-specific tolerance to chronic dopamine receptor blockade. Proc. Soc. Neurosci., Vol. II, Part 2, 848 (1976)
Eichler, A. J., Antelman, S. M., Kairns, L.: Self stimulation: Evidence for tolerance to neuroleptics in the frontal cortex. Proc. Soc. Neurosci., Vol. III, 440 (1977)
Ettenberg, A., Milner, P. M.: Effects of dopamine supersensitivity on lateral hypothalamic self-stimulation in rats. Pharmacol. Biochem. Behav. 7, 507–514 (1977)
Fibiger, H. C.: Drugs and reinforcement mechanisms: a critical review of the catecholamine theory. Annu. Rev. Pharmacol. Toxicol. 18, 37–56 (1978)
Freeman, J. J., Sulser, R.: Iprindole-amphetamine interactions in the rat: The role of aromatic hydroxylation of amphetamine in its mode of action. J. Pharmacol. Exp. Ther. 183, 307–315 (1972)
Hökfelt, T., Ljungdahl, A., Fuxe, K., Johansson, O.: Dopamine nerve terminals in the rat limbic cortex: aspects of the dopamine hypothesis of schizophrenia. Science 184, 177–179 (1974)
Janssen, P. A. J.: Chemical and pharmacological classification of neuroleptics. In: Modern problems of pharmacopsychiatry, vol. 5, D. P. Bobon, P. A. J. Janssen, J. Bobon, eds., pp. 33–44. New York: Karger 1970
Lerner, P., Nose, P., Gordon, E. K., Lovenberg, W.: Haloperidol: Effect of long-term treatment on rat striatal dopamine synthesis and turnover. Science 197, 181–183 (1977)
Leyson, J. D., Gommeren, W.: Different kinetic properties of neuroleptic receptor binding in the rat striatum and frontal cortex. Life Sci. 23, 447–452 (1978)
Leyson, J. D., Gommeren, W., Laduron, P. M.: Spiperone: A ligand of choice for neuroleptic receptors. Kinetics and characteristics of in vitro binding. Biochem. Pharmacol. 27, 307–316 (1978)
Mogenson, G. J., Takigawa, M., Robertson, A., Wu, M.: Self-stimulation of the nucleus accumbens septi and ventral tegmental area of Tsai attenuated by microinjections of spiroperidol into the nucleus accumbens septi. Brain Res. 171, 247–259 (1979)
Mora, F.: The neurochemical substrates of prefrontal cortex self-stimulation: A review and an interpretation of some recent data. Life Sci. 22, 919–930 (1978)
Robertson, A., Mogenson, G. J.: Evidence for a role for dopamine in self-stimulation of the nucleus accumbens of the rat. Can. J. Psychol. 32, 67–76 (1978)
Rolls, E. T., Rolls, B. J., Kelly, P. H., Shaw, S. G., Dale, R.: The relative attenuation of self stimulation, eating and drinking produced by dopamine-receptor blockade. Psychopharmacologia (Berl.) 38, 219–230 (1974)
Scatton, B., Glowinski, J., Julou, L.: Dopamine metabolism in the mesolimbic and mesocortical dopaminergic systems after single and repeated administrations of neuroleptics. Brian Res. 109, 184–189 (1976)
Snyder, S. H., Banarjee, S. P., Yamamura, H. I., Greenberg, C.: Drugs, neurotransmitters and schizophrenia. Science 184, 1243–1253 (1974)
Stein, L.: Self-stimulation of the brain and the central stimulant action of amphetamine. Fed. Proc. 23, 836–850 (1964)
Wauquier, A., Rolls, E. T.: Brain stimulation reward. Amsterdam: North Holland 1976
Wise, R. A.: Catecholamine theories of reward: A critical review. Brain Res. 152, 215–247 (1978)
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Robertson, A., Mogenson, G.J. Facilitation of self-stimulation of the prefrontal cortex in rats following chronic administration of spiroperidol or amphetamine. Psychopharmacology 65, 149–154 (1979). https://doi.org/10.1007/BF00433041
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DOI: https://doi.org/10.1007/BF00433041