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Titolo:
Increased responsiveness of dopamine to atypical, but not typical antipsychotics in the medial prefrontal cortex of rats reared in isolation
Autore:
Heidbreder, CA; Foxton, R; Cilia, J; Hughes, ZA; Shah, AJ; Atkins, A; Hunter, AJ; Hagan, JJ; Jones, DNC;
Indirizzi:
GlaxoSmithKline Pharmaceut, Ctr Excellence Drug Discovery Psychiat, HarlowCM19 5AW, Essex, England GlaxoSmithKline Pharmaceut Harlow Essex England CM19 5AW , Essex, England GlaxoSmithKline Pharmaceut, Ctr Excellence Drug Discovery Neurol, Harlow CM19 5AW, Essex, England GlaxoSmithKline Pharmaceut Harlow Essex England CM19 5AW , Essex, England GlaxoSmithKline Pharmaceut, Computat & Struct Sci Mass Spectrometry, Harlow CM19 5AW, Essex, England GlaxoSmithKline Pharmaceut Harlow Essex EnglandCM19 5AW , Essex, England GlaxoSmithKline Pharmaceut, Dept Drug Dependence Res, Ctr Excelence Drug Discovery Psychiat, Harlow CM19 5AW, Essex, England GlaxoSmithKline Pharmaceut Harlow Essex England CM19 5AW , Essex, England
Titolo Testata:
PSYCHOPHARMACOLOGY
fascicolo: 2-3, volume: 156, anno: 2001,
pagine: 338 - 351
Fonte:
ISI
Lingua:
ENG
Soggetto:
PREPULSE INHIBITION DEFICITS; 5-HT1A RECEPTOR ACTIVATION; EXCITATORY AMINO-ACIDS; NITRIC-OXIDE; SCHIZOPHRENIC-PATIENTS; NUCLEUS-ACCUMBENS; SOCIAL-ISOLATION; DOUBLE-BLIND; N-ACETYLASPARTATE; ACOUSTIC STARTLE;
Keywords:
antipsychotic drug; dopamine; amino acid; social isolation syndrome; PPI; medial prefrontal cortex;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
89
Recensione:
Indirizzi per estratti:
Indirizzo: Heidbreder, CA GlaxoSmithKline Pharmaceut, Ctr Excellence Drug Discovery Psychiat, New Frontiers Sci Pk N, Harlow CM19 5AW, Essex, England GlaxoSmithKline Pharmaceut New Frontiers Sci Pk N Harlow Essex England CM19 5AW
Citazione:
C.A. Heidbreder et al., "Increased responsiveness of dopamine to atypical, but not typical antipsychotics in the medial prefrontal cortex of rats reared in isolation", PSYCHOPHAR, 156(2-3), 2001, pp. 338-351

Abstract

Dopaminergic hypofunction in the medial prefrontal cortex (mPFC) has teen associated with the aetiology of negative symptoms and cognitive dysfunction of schizophrenia, which are both alleviated by clozapine and other atypical antipsychotics such as olanzapine. In rodents, early life exposure to stressful experiences such as social isolation produces a spectrum of symptoms emerging in adult life, which can be restored by antipsychotic drugs. Thepresent series of experiments sought to investigate the effect of clozapine (5-10 mg/kg SC), olanzapine (5 mg/kg SC), and haloperidol (0.5 mg/kg SC) on dopamine (DA) and amino acids in the prelimbic/infralimbic subregion of the mPFC in group- and isolation-reared rats. Rats reared in isolation showed significant and robust deficits in prepulse inhibition of the acoustic startle. In group-reared animals, both clozapine and olanzapine produced a significant increase in DA outflow in the mPFC. Isolation-reared rats showeda significant increase in responsiveness to both atypical antipsychotics compared with group-reared animals. In contrast, the administration of haloperidol failed to modify dialysate DA levels in mPFC in either group- or isolation-reared animals. The results also show a positive relationship between the potency of the tested antipsychotics to increase the release of DA inthe mPFC and their respective affinities for 5-HT1A relative to DA D-2 or D-3 receptors. Finally, isolation-reared rats showed enhanced neurochemicalresponses to the highest dose of clozapine as indexed by alanine, aspartate, GABA, glutamine, glutamate, histidine, and tyrosine. The increased DA responsiveness to the atypical antipsychotic drugs clozapine and olanzapine may explain, at least in part, clozapine- and olanzapine-induced reversal ofsome of the major behavioral components of the social isolation syndrome, namely hyperactivity and attention deficit.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 29/01/20 alle ore 18:54:20