Abstract
The behavioral effects of low doses of the catecholamine (CA) synthesis inhibitor, α-methyl-p-tyrosine (α-MPT, 50 mg/kg i.p.), or the norepinephrine (NE) synthesis inhibitors (FLA-63, 15 mg/kg i.p., U-14624, 50 mg/kg i.p., or disulfiram, 150 mg/kg i.p.) were studied in rats pretreated with reserpine (1 mg/kg i.p.) 24 h before. Rats were implanted either in the area ventralis tegmenti (AVT) or in the lateral hypothalamus (LH). The modifications of CA synthesis and endogenous CA levels were estimated in a parallel experiment. Reserpine treatment produced a slow decrease in self-stimulation (SS) rates during the first 12 h; SS rates were 85% of control values 24 h after reserpine treatment. Injection of α-MPT in reserpine-pretreated rats inhibited SS (85% decrease 3 h after administration either in AVT or LH rats), whereas dopamine Β-hydroxylase inhibition had no great effect on SS. The administration of very low doses of α-MPT (20 mg/kg i.p.) to rats treated with reserpine (24 h before) plus FLA-63 (1 h before) induced an important decrease in SS rates in AVT-implanted rats only. The major conclusion is that dopaminergic neurons seem to be involved in AVT and LH SS. The last experiment suggests the involvement of a balance between dopaminergic and noradrenergic neurons in AVT SS.
Similar content being viewed by others
References
Arbuthnott, G. W., Fuxe, K., Ungerstedt, U.: Central catecholamine turnover and self-stimulation behavior. Brain Res. 27, 406–413 (1971)
Black, W. C., Cooper, B. R.: Reduction of electrically rewarded behavior by interference with monoamine synthesis. Physiol. Behav. 5, 1405–1409 (1970)
Broekkamp, C. L. E., van Rossum, J. M.: Effects of apomorphine on self-stimulation behavior. Psychopharmacologia (Berl.) 34, 71–80 (1974)
Cooper, B. R., Black, W. C., Paolino, R. M.: Decreased septal forebrain and lateral hypothalamic reward after alphamethyl-p-tyrosine. Physiol. Behav. 6, 425–429 (1971)
Cooper, B. R., Grant, L. D., Breese, G. R.: Comparison of the behavioral depressant effects of biogenic amine depleting and neuroleptic agents following various 6-hydroxydopamine treatments. Psychopharmacologia (Berl.) 31, 95–109 (1973)
Crow, T. J.: A map of the rat mesencephalon for electrical self-stimulation. Brain Res. 36, 265–273 (1972)
Curzon, G., Green, A. R.: Rapid method for the determination of 5-hydroxytryptamine and 5-hydroxyindole-acetic acid in small regions of the rat brain. Brit. J. Pharmacol. 39, 653–655 (1970)
Edwards, A. L.: Experimental design in psychological research. New York: Holt, Rinehart and Winston 1970
von Euler, U. S., Lishajko, F.: Improved technic for the fluorimetric of catecholamines. Acta physiol. scand. 51, 348–355 (1961)
Franklin, K. B. J., Herberg, L. J.: Self-stimulation and catecholamines: drug-induced mobilization of the “reserve-pool” re-establishes responding in catecholamine-depleted rats. Brain Res. 67, 429–438 (1974)
German, D. C., Bowden, D. M.: Catecholamine systems as the neural substrate for intracranial self-stimulation: A hypothesis. Brain Res. 73, 381–419 (1974)
Glowinski, J., Axelrod, J., Iversen, L.: Regional studies of catecholamines in the rat brain. IV. Effects of drugs on the disposition and metabolism of 3H-norepinephrine and 3H-dopamine. J. Pharmacol. exp. Ther. 153, 30–41 (1966a)
Glowinski, J., Iversen, L. L., Axelrod, J.: Storage and synthesis of norepinephrine in the reserpine-treated rat brain. J. Pharmacol. exp. Ther. 151, 385–399 (1966b)
Goldstein, M., Nakajima, K.: The effect of disulfiram on catecholamine levels in the brain. J. Pharmacol. exp. Ther. 157, 96–102 (1967)
Javoy, F. M., Hammon, M., Glowinski, J.: Disposition of newly synthetized amines in cell bodies and terminals of central catecholaminergic neurons. (I) Effects of amphetamines and thioproperazine on the metabolism of CA in the caudate nucleus, the substantia nigra and the ventromedial nucleus of the hypothalamus. Europ. J. Pharmacol. 10, 178–188 (1970)
Johnson, G. A., Boukma, S. J., Kim, E. G.: In vivo inhibition of dopamine beta-hydroxylase by 1-phenyl-3-(2-thiazolyl)-2-thiourea (U 14624). J. Pharmacol. exp. Ther. 171, 80–87 (1970)
Laverty, R., Taylor, K. M.: The fluorimetric assay of catecholamines and related compounds. Improvements on extensions to hydroxyindole technic. Ann. Biochem. 22, 269–279 (1968)
Liebman, J. M., Butcher, L. L.: Effects on self-stimulation of drugs influencing dopaminergic neurotransmission mechanisms. Naunyn-Schmiedeberg's Arch. Pharmacol. 277, 305–318 (1973)
Lippa, A. S., Antelman, S. M., Fischer, A. E., Canfield, D. R.: Neurochemical mediation of reward: A significant role for dopamine? Pharmacol. Biochem. Behav. 1, 23–28 (1973)
Moore, K. E.: Effects of disulfiram and diethyldithiocarbamate on spontaneous locomotor activity and brain catecholamine levels in mice. Biochem. Pharmacol. 18, 1627–1634 (1969)
Persson, T., Waldeck, B.: Further studies on the possible interaction between dopamine and noradrenaline containing neurons in the brain. Europ. J. Pharmacol. 11, 315–320 (1970)
Phillips, A. G., Brooke, S. M., Fibiger, H.: Effects of amphetamine isomers and neuroleptics on self-stimulation from the nucleus accumbens and dorsal noradrenergic bundle. Brain Res. 85, 13–22 (1975)
Phillips, A. G., Fibiger, H. C.: Dopaminergic and noradrenergic substrates of positive reinforcement: differential effects of d- and l-amphetamine. Science 179, 575–577 (1973)
Poschel, B. P. H., Ninteman, F. W.: Hypothalamic self-stimulation: its suppression by blockade of norepinephrine biosynthesis and reinstatement by metaamphetamine. Life Sci. 5, 11–16 (1966)
Prado-Alcala, R. A., Kent, E. W., Reid, L. D.: Intracranial self-stimulation effects along the route of the nigro-striatal bundle. Brain Res. 84, 531–540 (1975)
Rech, R. H., Carr, L. A., Moore, K. E.: Behavioral effects of α-methyltyrosine after prior depletion of brain catecholamines. J. Pharmacol. exp. Ther. 160, 326–335 (1968)
Ritter, S., Stein, L.: Self-stimulation in the mesencephalic trajectory of the ventral noradrenergic bundle. Brain Res. 81, 145–158 (1974)
Roll, S. K.: Intracranial self-stimulation and wakefulness: effect of manipulating ambient brain catecholamines. Science 168, 1370–1372 (1970)
St Laurent, J., Leclerc, R. R., Mitchell, M. L., Miliaressis, T. E.: Effects of apomorphine on self-stimulation. Pharmacol. Biochem. Behav. 1, 581–585 (1973)
Spector, S., Sjoredsma, A., Udenfriend, S.: Blockade of endogenous norepinephrine synthesis by α-methylparatyrosine an inhibitor of tyrosine hydroxylase. J. Pharmacol. exp. Ther. 147, 86–95 (1965)
Stein, L., Wise, C. D.: Release of norepinephrine from hypothalamus and amygdala by reward MFB stimulation and amphetamine. J. comp. physiol. Psychol. 67, 189–198 (1969)
Stinus, L., Le Moal, M., Cardo, B.: Autostimulation et catecholamines. I. Intervention possible de deux ≪compartiments≫ (compartiment fonctionnel et compartiment de réserve). Physiol. Behav. 9, 175–182 (1972)
Stinus, L., Thierry, A. M.: Self-stimulation and catecholamines. II. Blockade of self-stimulation by treatment with alpha-methylparatyrosine and the reinstatement by catecholamine precursor administration. Brain Res. 64, 189–198 (1973)
Stinus, L., Thierry, A. M., Blanc, G., Glowinski, J., Cardo, B.: Self-stimulation and catecholamines. III. Effect of imposed or self-stimulation in the area ventralis tegmenti or catecholamine utilization in the rat brain. Brain Res. 64, 199–210 (1973)
Stinus, L., Thierry, A. M., Cardo, B.: Self-stimulation and local injections of 6-hydroxydopamine into the rat brain: enhanced behavioral depressive effects of alpha-methylparatyrosine. Pharmacol. Biochem. Behav. 3, 19–24 (1975)
Svensson, T. H.: Increased dopamine concentration in the striatum in the mouse by Fla-63, a dopamine betahydroxylase inhibitor. J. Pharm. Pharmacol. 25, 73–75 (1973)
Thierry, A. M., Stinus, L., Blanc, G., Glowinski, J.: Some evidence for the existence of dopaminergic neurons in the rat cortex. Brain Res. 50, 230–234 (1973)
Vetulani, J., Reichenberg, K., Wiszniowska, G., Marchaj, J.: The effect of dopamine beta-hydroxylase inhibitors, dimethylphenylthiourea and fusaric acid, on locomotor and exploratory activity, body temperature and regional distribution of biogenic amines in the rat brain. Pol. J. Pharm. Pharmacol. 25, 559–572 (1973)
Wise, C. D., Stein, L.: Facilitation of brain self-stimulation by central administration of norepinephrine. Science 163, 299–301 (1969)
Wauquier, A., Niemegeers, C. J. E.: Intracranial self-stimulation in rats as a function of various stimulus parameters. II. Influence of haloperidol, pimozide and pipamperone on MFB stimulation with monopolar electrodes. Psychopharmacologia (Berl.) 27, 191–202 (1972)
Wauquier, A., Niemegeers, C. J. E.: Intracranial self-stimulation in rats as a function of various parameters. III. Influence of apomorphine on MFB stimulation with monopolar electrodes. Psychopharmacologia (Berl.) 30, 163–172 (1973)
Author information
Authors and Affiliations
Additional information
This investigation was supported by a Grant from the C.N.R.S. (E.R.A. No. 416).
Rights and permissions
About this article
Cite this article
Stinus, L., Thierry, A.M. & Cardo, B. Effects of various inhibitors of tyrosine hydroxylase and dopamine beta-hydroxylase on rat self-stimulation after reserpine treatment. Psychopharmacologia 45, 287–294 (1976). https://doi.org/10.1007/BF00421142
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF00421142