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Abstract

Alkylation of mu opioid receptors by beta-funaltrexamine in vivo: comparison of the effects on in situ binding and heroin self-administration in rats.

T J Martin, S I Dworkin and J E Smith
Journal of Pharmacology and Experimental Therapeutics March 1995, 272 (3) 1135-1140;
T J Martin
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S I Dworkin
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J E Smith
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Abstract

Mu opioid receptors are known to be directly involved in the reinforcing effects of opiates; however, little is known regarding the relationship between alteration of mu opioid receptor binding and opiate reinforcement. Intracerebroventricular (i.c.v.) administration of beta-funaltrexamine (beta-FNA) has been shown to reduce the number of mu opioid receptors throughout the brain and can be used to address questions regarding the relationship of the density of these receptors to the pharmacological effects of opiates. The time course of the effects of beta-FNA on heroin self-administration was compared with the effects on mu opioid receptor binding. beta-FNA (40 nmol) or saline was administered i.c.v. to animals trained to self-administer either 18 or 60 micrograms/kg per infusion of heroin. The number of infusions decreased after beta-FNA administration but steadily returned to base-line levels approximately 10 days after beta-FNA treatment. The time course of the effects of beta-FNA on mu opioid receptor binding was determined in separate groups of animals. beta-FNA treatment decreased the number of [3H]D-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin binding sites by 34 to 50% in rat brain sections; an effect that persisted for up to 18 days. The affinity was unaffected initially, but decreased in a linear manner from days 9 to 18 after beta-FNA administration. The return of heroin self-administration before the return of mu opioid receptor binding suggests that the recovery of mu opioid receptor function after beta-FNA treatment is more complex than merely synthesis of new receptors.

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Journal of Pharmacology and Experimental Therapeutics
Vol. 272, Issue 3
1 Mar 1995
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Abstract

Alkylation of mu opioid receptors by beta-funaltrexamine in vivo: comparison of the effects on in situ binding and heroin self-administration in rats.

T J Martin, S I Dworkin and J E Smith
Journal of Pharmacology and Experimental Therapeutics March 1, 1995, 272 (3) 1135-1140;

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Abstract

Alkylation of mu opioid receptors by beta-funaltrexamine in vivo: comparison of the effects on in situ binding and heroin self-administration in rats.

T J Martin, S I Dworkin and J E Smith
Journal of Pharmacology and Experimental Therapeutics March 1, 1995, 272 (3) 1135-1140;
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