Authors: Milanés1 M.V.¹; Rabadan J.V.¹; Marin M.T.²; Laorden M.L.¹

Source: Journal of Autonomic Pharmacology, Volume 18, Number 6, December 1998 , pp. 371-375(5)

Publisher: Wiley-Blackwell

Abstract:

Summary •

The present investigation was aimed at determining if chronic activation of - or -opioid receptors induce development of tolerance and dependence to -opioid agonists on the isolated left atria of the rat.

•

Tolerance to a -agonist (specific tolerance) was induced by chronic administration of U-50,488H, a selective -agonist (15 mg kg^-1 i.p. twice a day for 4 days). The animals were rendered tolerant to morphine by subcutaneous implantation of morphine pellets (75 mg per pellet) for 7 days.

•

Tolerance to U-50, 488H was observed after its chronic administration and was revealed as a rightward shift of the concentration-response curve, it was accompanied by a decrease in the maximum response and in the slope. Preparations from morphine-treated rats were not tolerant to the selective -agonist, that is, there was no cross-tolerance between - and -agonists.

•

Dependence to the -agonist was tested by administration in the organ bath of Mr-2266 (preferential -antagonist) or nor-binaltorphimine (nor-BNI; selective -antagonist). The administration in the organ bath of the -antagonists Mr-2266 or nor-BNI to preparations from U-50, 488H treated rats induced an increase in atrial force of contraction. In contrast, the administration of the -antagonists to preparations from control rats induced a decrease in atrial force of contraction.

•

These findings demonstrate that left atria from chronically U-50488H-treated rats exhibit tolerance to the negative inotropic effects of U-50, 488H as well as opioid withdrawal after nor-BNI.

Document Type: Research article

DOI: http://dx.doi.org/10.1046/j.1365-2680.1998.1860371.x

Affiliations: 1: Department of Physiology and Pharmacology, Unit of Pharmacology, University School of Medicine, Murcia, Spain 2: Department of Pharmacy and Pharmaceutics Technology, School of Pharmacy, Granada, Spain

Publication date: 1998-12-01

Related content

• In this: publication
• By this: publisher
• In this Subject: Pharmacology
• By this author: Milanés1 M.V. ;  Rabadan J.V. ;  Marin M.T. ;  Laorden M.L.

Website © Publishing Technology. Article copyright remains with the publisher, society or author(s) as specified within the article.

• Terms and conditions
• Privacy policy
• Information for advertisers