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Titolo:
EFFECT OF CYP2D1 INHIBITION ON THE BEHAVIORAL-EFFECTS OF D-AMPHETAMINE
Autore:
TOMKINS DM; OTTON SV; JOHARCHI N; BERNS T; WU D; CORRIGALL WA; SELLERS EM;
Indirizzi:
ADDICT RES FDN,BIOBEHAV RES DEPT,33 RUSSELL ST TORONTO ON M5S 2S1 CANADA UNIV TORONTO,DEPT PHARMACOL TORONTO ON CANADA UNIV TORONTO,DEPT MED TORONTO ON CANADA UNIV TORONTO,DEPT PSYCHIAT TORONTO ON CANADA
Titolo Testata:
Behavioural pharmacology
fascicolo: 2-3, volume: 8, anno: 1997,
pagine: 223 - 235
SICI:
0955-8810(1997)8:2-3<223:EOCIOT>2.0.ZU;2-8
Fonte:
ISI
Lingua:
ENG
Soggetto:
DISCRIMINATIVE STIMULUS PROPERTIES; INDIVIDUAL-DIFFERENCES; SPRAGUE-DAWLEY; RAT; DEBRISOQUINE; METABOLISM; DOPAMINE; SPARTEINE; OXIDATION; CODEINE;
Keywords:
AMPHETAMINE; BUDIPINE; DRUG DISCRIMINATION; HYPERACTIVITY; QUININE; RAT; SELF-ADMINISTRATION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
47
Recensione:
Indirizzi per estratti:
Citazione:
D.M. Tomkins et al., "EFFECT OF CYP2D1 INHIBITION ON THE BEHAVIORAL-EFFECTS OF D-AMPHETAMINE", Behavioural pharmacology, 8(2-3), 1997, pp. 223-235

Abstract

In rats, amphetamine (AMP) conversion to 4-OH-AMP is metabolized by CYP2D1, the rat equivalent of the human enzyme CYP2D6. To determine theimpact of impaired AMP metabolism on its behavioural effects, AMP-induced hyperactivity, AMP discrimination and AMP self-administration were examined in male Wistar rats with or without pretreatment with the CYP2D1 inhibitors quinine and budipine. In vivo, quinine (20 mg/kg) andbudipine (10 mg/kg) increased the plasma area under the curve of AMP ii-fold and 3.6-fold respectively, and decreased the plasma levels of LL-OH-AMP, 3-fold and 8.6-fold, confirming that the doses used suppressed CYP2D1 activity. Both inhibitors prolonged AMP-induced hyperactivity (0.3 mg/kg) and prolonged the duration of AMP-appropriate responding for periods of up to 90 min post-AMP administration in a drug discrimination procedure. In rats given a preload dose of AMP (0.8 mg/kg) 3 h prior to the self-administration test session, CYP2D1 inhibition resulted in fewer AMP infusions being taken compared with rats receiving the AMP preload dose alone. These studies indicate that AMP is responsible for the behavioural effects seen in rats and that a rat phenocopymodel of the human CYP2D6 deficiency state can be produced by CYP2D1 inhibitors.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 02/07/20 alle ore 21:14:20