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Titolo:
An animal model of extrapyramidal side effects induced by antipsychotic drugs: Relationship with D2 dopamine receptor occupancy
Autore:
Crocker, AD; Hemsley, KM;
Indirizzi:
Flinders Univ S Australia, Dept Clin Pharmacol, Bedford Pk, SA 5001, Australia Flinders Univ S Australia Bedford Pk SA Australia 5001 SA 5001, Australia Flinders Univ S Australia, Ctr Neurosci, Bedford Pk, SA 5001, Australia Flinders Univ S Australia Bedford Pk SA Australia 5001 SA 5001, Australia
Titolo Testata:
PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY
fascicolo: 3, volume: 25, anno: 2001,
pagine: 573 - 590
SICI:
0278-5846(200104)25:3<573:AAMOES>2.0.ZU;2-S
Fonte:
ISI
Lingua:
ENG
Soggetto:
SUBSTANTIA-NIGRA; MUSCLE TONE; SIGMA-RECEPTORS; TIME-COURSE; IN-VIVO; CLOZAPINE; HALOPERIDOL; SITES; MOTOR; PET;
Keywords:
antipsychotic drugs; catalepsy; dopamine D2 receptors; EMG; extrapyramidal side effects; fluphenazine; haloperidol; muscle rigidity; receptor occupancy; striatum; substantia nigra; thioridazine;
Tipo documento:
Review
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
38
Recensione:
Indirizzi per estratti:
Indirizzo: Crocker, AD Flinders Univ S Australia, Dept Clin Pharmacol, GPO Box 2100, Bedford Pk, SA 5001, Australia Flinders Univ S Australia GPO Box 2100 Bedford Pk SA Australia 5001
Citazione:
A.D. Crocker e K.M. Hemsley, "An animal model of extrapyramidal side effects induced by antipsychotic drugs: Relationship with D2 dopamine receptor occupancy", PROG NEUR-P, 25(3), 2001, pp. 573-590

Abstract

1. Muscle rigidity was assessed quantitatively and objectively as increases in electromyographic (EMG) activity (muscle rigidity) in the hindlimb muscles of the rat following subcutaneous administration of haloperidol, fluphenazine and thioridazine.2. Behavioural changes were assessed as increases in the catalepsy score, defined as the time taken for an animal to move off an inclined grid.3. Increased tonic EMG activity, or the presence of catalepsy was related to the level of occupancy of dopamine D2 receptors in the striatum and substantia nigra of the brain, measured using ex vivo quantitative autoradiography.4. Increases in tonic EMG activity and the induction of catalepsy were associated with >80% occupancy of striatal and nigral D2 receptors by fluphenazine, while haloperidol increased tonic EMG activity at D2 occupancies of >57%.5. Thioridazine at doses ranging from 1-15mg/kg failed to increase EMG activity and occupied <61% of striatal D2 receptors.6. Overall the findings support the hypothesis that muscle rigidity is observed when a threshold level of D2 receptors in the striatum and substantianigra are occupied by antipsychotic drugs.7. This conclusion is consistent with the results of positron emission tomography (PET) studies in humans, and those from our past studies in rats using raclopride, chlorpromazine and clozapine, in which a threshold of <similar to>70% striatal and nigral D2 receptor occupancy has been demonstrated.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 18/01/20 alle ore 07:22:27