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Discriminative stimulus produced by the imidazoline I2 site ligand, 2 -BFI

Lawrence Berkeley Laboratory, Center for Functional Imaging, University of California, Berkeley, CA 94720, USA

H.C. Jackson

Knoll Pharmaceuticals, Research Department, Nottingham NG2 3AA

D.J. Nutt

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

S.L. Handley

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

2-(2-Benzofuranyl)-2-imidazoline, RX801077 (2-BFI) which has high affinity for imidazoline I₂ binding sites and very low aflinity for ₂-adrenoceptors, has been investigated for its ability to produce a discriminative stimulus (cue) in drug-discrimination studies in rats since the existence of such a cue could assist in determining the functionality of I₂ sites. All rats subjected to training proved able to discriminate the training dose of 2-BFI (33 µmol/kg i.p) from saline vehicle and lower (5-14 µmol/kg) doses exhibited dose-dependent substitution. The mixed ₂-adrenoceptor/I ₂ site ligand idazoxan fully substituted at 40µmol/kg. However, ethoxy idazoxan (11 µmol/kg) and fluparoxan (13 µmol/kg), selective ₂-adrenoceptor antagonists, also fully substituted for 2- BFI as did the monoamine oxidase (MAO) inhibitors moclobemide (99 µmol/kg) and pargyline (153 µmol/kg). A lower dose of moclobemide (16 µmol/kg) exhibited partial substitution. The ₂-adrenoceptor agonists clonidine (0.1 µmol/kg) and guanabenz (1.4 µmol/kg), and the benzodiazepine diazepam (14 µmol/kg), failed to substitute for 2-BFI indicating cue specificity. However, 2-BFI (14-50 µmol/kg) substituted partially but dose-dependently for clonidine (0.1 µmol/kg) in rats trained to distinguish the latter from saline. Changes in rates of response were independent of the degree of substitution. The observed pattern of drug substitution is consistent with the previously reported ability of 2-BFI to decrease MAO activity and thus increase extracellular monoamines.

Key Words: 2-BFI • drug discrimination • imidazoline I2 binding sites • 2-adrenoceptor antagonists • monoamine oxidase inhibitors

Journal of Psychopharmacology, Vol. 10, No. 4, 273-278 (1996)
DOI: 10.1177/026988119601000403


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