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Titolo:
Antagonism of the discriminative stimulus effects of cocaine at two training doses by dopamine D2-like receptor antagonists
Autore:
Costanza, RM; Barber, DJ; Terry, P;
Indirizzi:
Univ Birmingham, Sch Psychol, Birmingham B15 2TT, W Midlands, England UnivBirmingham Birmingham W Midlands England B15 2TT W Midlands, England
Titolo Testata:
PSYCHOPHARMACOLOGY
fascicolo: 2, volume: 158, anno: 2001,
pagine: 146 - 153
Fonte:
ISI
Lingua:
ENG
Soggetto:
PHARMACOLOGICAL CHARACTERIZATION; SQUIRREL-MONKEYS; RHESUS-MONKEYS; D-AMPHETAMINE; RATS; AGONISTS; MEDIATION; D-2; INVOLVEMENT; SUBTYPES;
Keywords:
cocaine; D1-like receptor; D2-like receptor; drug discrimination; L-741,626; haloperidol; raclopride; rat;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
51
Recensione:
Indirizzi per estratti:
Indirizzo: Terry, P Univ Birmingham, Sch Psychol, Birmingham B15 2TT, W Midlands, England Univ Birmingham Birmingham W Midlands England B15 2TT s, England
Citazione:
R.M. Costanza et al., "Antagonism of the discriminative stimulus effects of cocaine at two training doses by dopamine D2-like receptor antagonists", PSYCHOPHAR, 158(2), 2001, pp. 146-153

Abstract

Rationale: The relative contributions of different dopamine receptor subtypes to the discriminative stimulus effects of cocaine may be influenced by the training dose of cocaine. Substitution tests with dopamine receptor agonists have suggested that the role of dopamine D2-like receptors is diminished relative to that of D1-like receptors at a training dose of 3 mg/kg cocaine compared with a training dose of 10 mg/kg. Objectives: To test whetherdopamine D2-like receptor antagonists were differentially effective at attenuating cocaine's discriminative stimulus effects at different training doses, and to test for the first time an antagonist that is selective for thedopamine D2 receptor within the D2-like receptor subfamily. Methods: Rats were trained to press one lever after receiving cocaine and another after receiving saline (maintaining >95% drug-appropriate responding). Three dopamine D2-like receptor antagonists (haloperidol, raclopride and L-741,626) were tested in rats trained at 3 mg/kg or 10 mg/kg cocaine. At the lower training dose, the D1-like receptor antagonist SCH 39166 was also tested. Results: The antagonists were not differentially effective between training groups: they all produced parallel, rightward shifts in cocaine's dose-effect function. indicating surmountable antagonism. Conclusions: The results demonstrate that D2-like receptor antagonists with different affinities for the various D2-like receptors can antagonise the discriminative stimulus effects of cocaine at two training doses. Importantly, antagonism by L-741,626 implies that stimulation of D2 receptors alone (not D3 or D4 receptors) is sufficient to mediate cocaine's discriminative stimulus effects. Finally, theclaim that D1-like receptors are preferentially involved at low training doses of cocaine is only consistent with the current findings if indirect stimulation of D2 receptors by low doses of cocaine remains necessary for theexpression of the D1-like receptor-mediated effect.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 03/06/20 alle ore 08:59:35