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The Journal of Neuroscience, June 15, 2001, 21(12):4436-4442

Endomorphin-1: Induction of Motor Behavior and Lack of Receptor Desensitization

Arpesh Mehta¹, George Bot², Terry Reisine², and Marie-Françoise Chesselet¹

¹ Department of Neurology, University of California, Los Angeles School of Medicine, Los Angeles, California 90095, and ² Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104

The endomorphins are recently discovered endogenous agonists for the µ-opioid receptor (Zadina et al., 1997). Endomorphins produce analgesia; however, their role in other brain functions has not been elucidated. We have investigated the behavioral effects of endomorphin-1 in the globus pallidus, a brain region that is rich in µ-opioid receptors and involved in motor control. Bilateral administration of endomorphin-1 in the globus pallidus of rats induced orofacial dyskinesia. This effect was dose-dependent and at the highest dose tested (18 pmol per side) was sustained during the 60 min of observation, indicating that endomorphin-1 does not induce rapid desensitization of this motor response. In agreement with a lack of desensitization of µ-opioid receptors, 3 hr of continuous exposure of the cloned µ receptor to endomorphin-1 did not diminish the subsequent ability of the agonist to inhibit adenylate cyclase activity in cells expressing the cloned µ-opioid receptor. Confirming the involvement of µ-opioid receptors, the behavioral effect of endomorphin-1 in the globus pallidus was blocked by the opioid antagonist naloxone and the µ-selective peptide antagonist Cys²-Tyr³-Orn⁵-Pen⁷ amide (CTOP). Furthermore, the selective µ receptor agonist [D-Ala²-N-Me-Phe⁴-Glycol⁵]-enkephalin (DAMGO) also stimulated orofacial dyskinesia when infused into the globus pallidus, albeit transiently. Our findings suggest that endogenous µ agonists may play a role in hyperkinetic movement disorders by inducing sustained activation of pallidal opioid receptors.

Key words: µ-opioid receptors; dyskinesia; globus pallidus; cAMP; adenylate cyclase; movement disorders

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Copyright © 2001 Society for Neuroscience  0270-6474/01/21124436-07$05.00/0

This article has been cited by other articles:

				J. Fichna, A. Janecka, J. Costentin, and J.-C. Do Rego The Endomorphin System and Its Evolving Neurophysiological Role Pharmacol. Rev., March 1, 2007; 59(1): 88 - 123. [Abstract] [Full Text] [PDF]

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