ABT-418 : discriminative stimulus properties and effect on ventral tegmental cell activity
In: Psychopharmacologia, Jg. 119 (1995), Heft 4, S. 368-375
Online
academicJournal
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Zugriff:
Previous studies have established that ABT-418 [(S)-3-methyl-5-(1 methyl-2-pyrrolidinyl)isoxazole hydrochloride] is a novel neuronal nicotinic acetylcholine receptor (nAChR) ligand with cognitive enhancing and anxiolytic-like activity 3- to 10-fold more potent than (-)-nicotine in rodents. A series of experiments was conducted to determine the discriminative stimulus properties of ABT-418 in comparison with (-)-nicotine, and to determine the relative potencies of these compounds on ventral tegmental area (VTA) neurons. While rats were able to discriminate ( - )-nicotine 1.9 μmol/kg in 39 days, they were not able to discriminate 1.9 or 6.2 μmol/kg ABT-418 from a saline solution during 50 days of training. In rats trained to discriminate 1.9 μmol/kg (-)-nicotine, a reduced generalization was induced by ABT-418 at 1.9 and 6.2 μmol/kg, an effect completely blocked by the cholinergic channel blocker mecamylamine (15 μmol/l kg, IP). However, in extensively trained rats, intraperitoneal or subcutaneous injections of ABT-418 induced 78-82% generalization at the 6.2 μmol/kg dose. The predominant metabolites of ( - )-nicotine and ABT-418 (cotinine and A-87770, respectively) were devoid of any effect in nicotine-trained rats. The reduced potency of ABT-418 in nicotine-trained rats is consistent with the electrophysiological findings showing that ABT-418 is 3-fold less potent than (-)-nicotine in activating dopamine-containing neurons in the VTA area.
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ABT-418 : discriminative stimulus properties and effect on ventral tegmental cell activity
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Autor/in / Beteiligte Person: | BRIONI, J. D ; KIM, D. J. B ; BRODIE, M. S ; DECKER, M. W ; ARNERIC, S. P |
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Zeitschrift: | Psychopharmacologia, Jg. 119 (1995), Heft 4, S. 368-375 |
Veröffentlichung: | Berlin: Springer, 1995 |
Medientyp: | academicJournal |
Umfang: | print; 1 p.1/4 |
ISSN: | 0033-3158 (print) |
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