QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: jpet.106.118067v1 321/1/334    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Tanda, G. Articles by Katz, J. L. Search for Related Content PubMed PubMed Citation Articles by Tanda, G. Articles by Katz, J. L.

BEHAVIORAL PHARMACOLOGY

Effects of Muscarinic M₁ Receptor Blockade on Cocaine-Induced Elevations of Brain Dopamine Levels and Locomotor Behavior in Rats

Psychobiology (G.T., A.L.E., T.A.K., L.M.E., B.L.C., J.L.K.) and Medicinal Chemistry (A.H.N.) Sections, Medications Discovery Research Branch, Department of Health and Human Services, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland

Cholinergic muscarinic systems have been shown to influence dopaminergic function in the central nervous system. In addition, previous studies of benztropine analogs that inhibit dopamine uptake and show antagonism at muscarinic receptors show these drugs to be less effective than cocaine in producing its various prototypic effects such as locomotor stimulation. Because previous pharmacological studies on these topics have used nonselective M₁ antagonists, we examined the interactions of preferential M₁ muscarinic antagonists and cocaine. Dose-dependent increases in extracellular levels of dopamine in selected brain areas, the nucleus accumbens (NAc) shell and core, and the prefrontal cortex, were produced by cocaine but not by the preferential M₁ antagonists telenzepine and trihexyphenidyl. When administered with cocaine, however, both M₁ antagonists dose-dependently increased the effects of cocaine on dopamine in the NAc shell, and these effects were selective in that they were not obtained in the NAc core or in the prefrontal cortex. Telenzepine also increased locomotor activity, although the effect was small compared with that of cocaine. The locomotor stimulant effects of trihexyphenidyl, in contrast, approached those of cocaine. Telenzepine attenuated, whereas trihexyphenidyl enhanced the locomotor stimulant effects of cocaine, with neither drug facilitating cocaine-induced stereotypy. The present results indicate that preferential antagonist effects at muscarinic M₁ receptors do not uniformly alter all of the effects of cocaine, nor do they explain the differences in effects of cocaine and benztropine analogs, and that the alterations in dopamine levels in the NAc shell do not predict the behavioral effects of the interactions with cocaine.

Address correspondence to: Dr. Gianluigi Tanda, Department of Health and Human Services, National Institute on Drug Abuse, National Institutes of Health, Intramural Research Program, Medications Discovery Research Branch, Psychobiology Section, 5500 Nathan Shock Dr., Baltimore, MD 21224. E-mail: gtanda{at}intra.nida.nih.gov

This article has been cited by other articles:

				G. Tanda, A. H. Newman, A. L. Ebbs, V. Tronci, J. L. Green, R. J. Tallarida, and J. L. Katz Combinations of Cocaine with Other Dopamine Uptake Inhibitors: Assessment of Additivity J. Pharmacol. Exp. Ther., September 1, 2009; 330(3): 802 - 809. [Abstract] [Full Text] [PDF]

				Z. Li, A. J. Prus, J. Dai, and H. Y. Meltzer Differential Effects of M1 and 5-Hydroxytryptamine1A Receptors on Atypical Antipsychotic Drug-Induced Dopamine Efflux in the Medial Prefrontal Cortex J. Pharmacol. Exp. Ther., September 1, 2009; 330(3): 948 - 955. [Abstract] [Full Text] [PDF]

				A. A. Othman, A. H. Newman, and N. D. Eddington Applicability of the Dopamine and Rate Hypotheses in Explaining the Differences in Behavioral Pharmacology of the Chloro-Benztropine Analogs: Studies Conducted Using Intracerebral Microdialysis and Population Pharmacodynamic Modeling J. Pharmacol. Exp. Ther., August 1, 2007; 322(2): 760 - 769. [Abstract] [Full Text] [PDF]