Abstract
Intravenous self-administration of d-amphetamine (0.25 mg/kg/injection) decreased in a dose-related fashion after injections of the dopaminergic agonists apomorphine and piribedil. The dopaminergic agonists appear to suppress amphetamine intake in the same way as do ‘free’ amphetamine injections, by extending drug satiation in a given interresponse period. Clonidine, an alpha noradrenergic agonist, did not have similar effects. Apomorphine and piribedil did not increase 14C-amphetamine levels in rat brains, nor did they retard disappearance of 14C-amphetamine; thus their amphetamine-like effects are not due to alterations of amphetamine metabolism. Rats responding for amphetamine continued to respond for apomorphine or piribedil when the latter drugs were substituted for the former. Rats experienced in amphetamine self-administration readily initiated and maintained responding for apomorphine and piribedil. The dopaminergic blocker (+)-butaclamol disrupted responding for apomorphine and piribedil, although it produced no marked increase in responding for the dopaminergic agonists, as it does for amphetamine. These data add to the evidence that actions in the dopaminergic synapse account for amphetamine's reinforcing properties.
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References
Andén, N.-E., Rubenson, A., Fuxe, K., Hökfelt, T.: Evidence for dopamine receptor stimulation by apomorphine. J. Pharm. Pharmacol. 19, 627–629 (1967)
Axelrod, J.: Studies on sympathomimetic amines. II. The biotransformation and physiological disposition of d-amphetamine, d-p-hydroxyamphetamine and d-methamphetamine. J. Pharmacol. Exp. Ther. 110, 315–326 (1954)
Balster, R. L., Schuster, C. R.: A comparison of d-amphetamine, l-amphetamine, and methamphetamine self-administration in rhesus monkey. Pharmacol. Biochem. Behav. 1, 67–71 (1973)
Baxter, B. L., Gluckman, M. I., Stein, L., Scerni R. A.: Self-injection of apomorphine in the rat: positive reinforcement by a dopamine receptor stimulant. Pharmacol. Biochem. Behav. 2, 387–391 (1974)
Baxter, B. L., Gluckman, M. I., Scerni, R. A.: Apomorphine self-injection is not affected by alpha-methylparatyrosine treatment: support for dopaminergic reward. Pharmacol. Biochem. Behav. 4, 611–612 (1976)
Corrodi, H., Farnebo, L.-O., Fuxe, K., Hamberger, B., Ungerstedt, U.: ET 495 and brain catecholamine mechanisms: evidence for stimulation of dopamine receptors. Eur. J. Pharmacol. 20, 195–204 (1972)
Davis, W. M., Smith, S. G.: Effect of haloperidol on (+) amphetamine self-administration. J. Pharm. Pharmacol 27, 540–542 (1975)
Davis, W. M., Smith, S. G.: Catecholaminergic mechanisms of reinforcement: direct assessment by drug self-administration. Life Sci. 20, 483–492 (1977)
Davis, W. M., Smith, S. G., Khalsa, J. H.: Noradrenergic role in the self-administration of morphine or amphetamine. Pharmacol. Biochem. Behav. 2, 477–484 (1975)
Deneau, G., Yanagita, T., Seevers, M. H.: Self-administration of psychoactive substances by the monkey: a measure of psychological dependence. Psychopharmacologia (Berl.) 16, 30–48 (1969)
deWit, H., Wise, R. A.: Blockade of cocaine reinforcement in rats with the dopamine receptor blocker pimozide, but not with noradrenergic blockers phentolamine and phenoxybenzamine. Can. J. Psychol. 31, 195–203 (1977)
Götestam, K. G., Andersson, B. E.: Assessment of reinforcing properties of amphetamine analogues in self-administering rats. Postgrad. Med. J. 51 (Suppl. 1), 80–83 (1975)
Griffiths, R. R., Winger, G., Brady, J. V., Snell, J. D.: Comparison of behavior maintained by infusions of eight phenylethylamines in baboons. Psychopharmacology 50, 251–258 (1976)
Gunne, L. M., Änggård, E., Jönsson, L. E.: Clinical trials with amphetamine-blocking drugs. Psychiatr. Neurol. Neurochir. 75, 225–226 (1972)
Hoffmeister, F., Schlichting, U. U.: Reinforcing properties of some opiates and opioids in rhesus monkeys with histories of cocaine and codeine self-administration. Psychopharmacologia (Berl.) 23, 55–74 (1972)
Kramer, J. C., Fischman, V. S., Littlefield, D. C.: Amphetamine abuse: pattern and effects of high doses taken intravenously. J. Am. Med. Assoc. 201, 305–309 (1967)
Lal, S., Sourkes, T. L., Missala, K.: The effects of certain tranquilisers, chlorpromazine metabolites and diethyldithiocarbamate on tissue amphetamine levels in the rat. Arch. Int. Pharmacodyn. 207, 122–130 (1974)
Lemberger, L., Witt, E. D., Davis, J. M., Kopin, I. J.: The effects of haloperidol and chlorpromazine on amphetamine metabolism and amphetamine stereotype behavior in the rat. J. Pharmacol. Exp. Ther. 174, 428–433 (1970)
Pickens, R., Meisch, R. A., Dougherty, J. A.: Chemical interactions in methamphetamine reinforcement. Psychol. Rep. 23, 1267–1270 (1968)
Pickens, R., Thompson, T.: Cocaine-reinforced behavior in rats: effects of reinforcement magnitude and fixed-ratio size. J. Pharmacol. Exp. Ther. 161, 122–129 (1968)
Risner, M. E.: Intravenous self-administration of d-and l-amphetamine by dog. Eur. J. Pharmacol. 32, 344–348 (1975)
Risner, M. E., Jones, B. E.: The role of noradrenergic and dopaminergic processes in amphetamine self-administration. Pharmacol. Biochem. Behav. 5, 477–482 (1976)
Shoeman, D. W., Sirtori, C. R., Azarnoff, D. L.: Inhibition of amphetamine tolerance and metabolism by propranolol. J. Pharmacol. Exp. Ther. 191, 68–71 (1974)
Voith, K., Herr, F.: The behavioral pharmacology of butaclamol hydrochloride (AY-23,028), a new potent neuroleptic drug. Psychopharmacologia (Berl.) 42, 11–20 (1975)
Wilson, M. C., Hitomi, M., Schuster, C. R: Psychomotor stimulant self-administration as a function of dosage per injection in the rhesus monkey. Psychopharmacologia (Berl.) 22, 271–281 (1971)
Wilson, M. C., Schuster, C. R.: The effects of chlorpromazine on psychomotor stimulant self-administration in the rhesus monkey. Psychopharmacologia (Berl.) 26, 115–126 (1972)
Wilson, M. C., Schuster, C. R.: The effects of stimulants and depressants on cocaine self-administration behavior in the rhesus monkey. Psychopharmacologia (Berl.) 31, 291–304 (1973)
Wilson, M. C., Schuster, C. R.: Mazindol self-administration in the rhesus monkey. Pharmacol. Biochem. Behav. 4, 207–210 (1976)
Wise, R. A., Yokel, R. A., deWit, H.: Both positive reinforcement and conditioned aversion from amphetamine and from apomorphine in rats. Science 191, 1273–1275 (1976)
Woods, J. H., Tessel, R. E.: Fenfluramine: amphetamine congener that fails to maintain drug-taking behavior in the rhesus monkey. Science 185, 1067–1069 (1974)
Yokel, R. A., Pickens, R.: Self-administration of optical isomers of amphetamine and methylamphetamine by rats. J. Pharmacol. Exp. Ther. 187, 27–33 (1973)
Yokel, R. A., Pickens, R.: Drug level of d- and l-amphetamine during intravenous self-administration. Psychopharmacologia (Berl.) 34, 255–264 (1974)
Yokel, R. A., Wise, R. A.: Increased lever pressing for amphetamine after pimozide in rats: implication for a dopamine theory of reward. Science 187, 547–549 (1975)
Yokel, R. A., Wise, R. A.: Attenuation of intravenous amphetamine reinforcement by central dopamine blockade in rats. Psychopharmacology 48, 311–318 (1976)
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Yokel, R.A., Wise, R.A. Amphetamine-type reinforcement by dopaminergic agonists in the rat. Psychopharmacology 58, 289–296 (1978). https://doi.org/10.1007/BF00427393
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DOI: https://doi.org/10.1007/BF00427393