A dopamine partial agonist and antagonist block amphetamine self-administration in a progressive ratio schedule

Citation
E. Izzo et al., A dopamine partial agonist and antagonist block amphetamine self-administration in a progressive ratio schedule, PHARM BIO B, 68(4), 2001, pp. 701-708
Citations number
29
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Neurosciences & Behavoir
Journal title
PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR
ISSN journal
0091-3057 → ACNP
Volume
68
Issue
4
Year of publication
2001
Pages
701 - 708
Database
ISI
SICI code
0091-3057(200104)68:4<701:ADPAAA>2.0.ZU;2-8
Abstract
A recently characterized class of compounds, dopamine partial agonists, hav e been suggested as potential therapeutic candidates for pharmacological in tervention in psychostimulant addiction. These drugs bind to dopamine recep tors with high affinity and low intrinsic activity and are thought to behav e as functional antagonists in conditions of high dopaminergic tone, and as agonists in conditions of low receptor occupancy by dopamine. The aim of t he present study was to characterize the effects of terguride, a partial do pamine agonist at the D2 receptor subtype, on intravenous self-administrati on of amphetamine in a progressive ratio schedule and to compare it with th e effects produced by the dopamine D2 antagonist eticlopride and the dopami ne D2 full agonist quinpirole. Terguride at the doses of 0.2 and 0.4 mg/ kg ip significantly decreased the maximum number of responses delivered for a single injection of amphetamine ("breaking point"), an effect similar to t hat produced by the antagonist eticlopride (0.01-0.1 mg/kg sc). In contrast , administration of quinpirole (0.1-1 mg/kg sc) did not significantly modif y the breaking point for amphetamine responding. Also. terguride dose-depen dently increased responding for amphetamine self-administration on a contin uous reinforcement schedule. These data further confirm the effects of terg uride on psychostimulant self-administration and indicate that under these conditions partial dopamine agonists act as functional dopamine receptor an tagonists. (C) 2001 Elsevier Science Inc. All rights reserved.