The involvement of alpha 2A-adrenoceptors in morphine analgesia, tolerance and withdrawal in mice.

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Ozdogan UK, Lahdesmaki J, Hakala K, Scheinin M

The involvement of alpha 2A-adrenoceptors in morphine analgesia, tolerance and withdrawal in mice.

Eur J Pharmacol. 2004 Aug 23;497(2):161-71.

PubMed ID

15306201 [ View in PubMed

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Abstract

Alpha(2)-adrenoceptor agonists potentiate opioid analgesia and alleviate opioid withdrawal. The effects of two alpha(2)-adrenoceptor agonists, clonidine (2 mg/kg) and dexmedetomidine (20 and 100 microg/kg), and the alpha(1)-adrenoceptor antagonist prazosin (0.5 mg/kg) were tested on morphine analgesia, tolerance, and withdrawal in wild-type and alpha(2A)-adrenoceptor knock-out (KO) mice. Analgesia and tolerance were assessed with the tail-flick test. Withdrawal was precipitated with naloxone. Prazosin potentiated morphine analgesia equally in both genotypes. Clonidine and dexmedetomidine had no analgesic effects in alpha(2A)-adrenoceptor KO mice, but morphine analgesia and tolerance were similar in both genotypes. Alpha(2A)-Adrenoceptor KO mice exhibited 70% fewer naloxone-precipitated jumps than wild-type mice; weight loss was similar in both genotypes. The alpha(2)-adrenoceptor agonists reduced opioid withdrawal signs only in wild-type mice. We conclude that alpha(2A)-adrenoceptors are not directly involved in morphine analgesia and tolerance, and not critical for potentiation of morphine analgesia by prazosin, but that alpha(2A)-adrenoceptors modulate the expression of opioid withdrawal signs in mice.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Clonidine	Alpha-2A adrenergic receptor	Protein	Humans	Yes	Agonist	Details
Dexmedetomidine	Alpha-2A adrenergic receptor	Protein	Humans	Yes	Agonist	Details