This Article Full Text (PDF) References Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Jordan, S. Articles by Handley, S.L. Search for Related Content PubMed Articles by Jordan, S. Articles by Handley, S.L. Social Bookmarking                         What's this?

Discriminative stimulus properties of ethoxy idazoxan

Pharmaceutical Sciences Institute, Aston University, Aston Triangle, Birmingham B4 7ET

H.C. Jackson

Psychopharmacology Unit, School of Medical Sciences, University Walk, Bristol BS8 1 TD, UK

D.J. Nutt

Psychopharmacology Unit, School of Medical Sciences, University Walk, Bristol BS8 1 TD, UK

S.L. Handley

Pharmaceutical Sciences Institute, Aston University, Aston Triangle, Birmingham B4 7ET

The technique of drug discrimination was used to examine the ability of the highly selective ₂-adrenoceptor antagonist ethoxy idazoxan, which has negligible affinity for ₁-adrenoceptors or I₂ imidazoline receptors, to produce an interoceptive discriminable stimulus or cue in rats. Rats were trained to respond on one lever after receiving -ethoxy idazoxan (2.5 mg/kg, i.p.) and on the opposite lever after saline vehicle. The ethoxy idazoxan cue appeared to be mediated by antagonists of central ₂-adrenoceptors, on the basis that dose- related substitution was produced by the highly selective ₂-adrenoceptor antagonists idazoxan (imidazoline), fluparoxan and 1-(2-pyrimidinyl) piperazine (1-PP) (both non-imidazoline) but not by clonidine, which acts as an agonist at this receptor, nor by the peripherally acting ₂-adrenoceptor antagonist L659,066. However, the ₂-adrenoceptor antagonists yohimbine and atipamezole showed partial and non-dose-dependent substitution for ethoxy idazoxan over a wide range of doses. 2-BFI [2-(2-benzfuranyl)-2-imidazoline, RX801077], an imidazoline which is highly selective for I₂ imidazoline receptors over ₂-adrenoceptors, showed dose- dependent substitution for ethoxy idazoxan, although the maximum effect (73% responding on the ethoxy idazoxan lever) fell short of criteria adopted for full substitution. Among other agents which bind to I₂ receptors, only idazoxan and 2-phenyl-2-imidazoline exhibited significant substitution; cirazoline could only be tested at very low doses because it powerfully inhibited responding in general, probably due to its ₁-adrenoceptor agonist properties. It is suggested that the ability of 2-BFI to substitute partially for ethoxy idazoxan might be due to the ability of both agents to increase extracellular concentrations of noradrenaline.

Key Words: ethoxy idazoxan • drug discrimination • 2-adrenoceptors • imidazoline I2 receptors

Journal of Psychopharmacology, Vol. 9, No. 3, 228-233 (1995)
DOI: 10.1177/026988119500900305


CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				S. Jordan, H.C. Jackson, D.J. Nutt, and S.L. Handley Discriminative stimulus produced by the imidazoline I2 site ligand, 2 -BFI J Psychopharmacol, January 1, 1996; 10(4): 273 - 278. [Abstract] [PDF]