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Titolo:
Early suppression of striatal cyclic GMP may pre-determine the induction and severity of chronic haloperidol-induced vacous chewing movements
Autore:
Bester, AM; Harvey, BH;
Indirizzi:
Potchefstroom Univ Christian Higher Educ, Fac Hlth Sci, Sch Pharm Pharmacol, ZA-2520 Potchefstroom, North West Prov, South Africa Potchefstroom Univ Christian Higher Educ Potchefstroom North West Prov South Africa ZA-2520
Titolo Testata:
METABOLIC BRAIN DISEASE
fascicolo: 4, volume: 15, anno: 2000,
pagine: 275 - 285
SICI:
0885-7490(200012)15:4<275:ESOSCG>2.0.ZU;2-L
Fonte:
ISI
Lingua:
ENG
Soggetto:
NITRIC-OXIDE SYNTHASE; METHYLENE-BLUE; IN-VIVO; TRANSMITTER RELEASE; ANTIPSYCHOTIC-DRUGS; HYDROGEN-PEROXIDE; BRAIN; CATALEPSY; RATS; NO;
Keywords:
haloperidol; extrapyramidal symptoms; tardive dyskinesia; nitric oxide; cGMP; methylene blue;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
37
Recensione:
Indirizzi per estratti:
Indirizzo: Harvey, BH Potchefstroom Univ Christian Higher Educ, Fac Hlth Sci, Sch Pharm Pharmacol, ZA-2520 Potchefstroom, North West Prov, South Africa Potchefstroom Univ Christian Higher Educ Potchefstroom North West Prov South Africa ZA-2520
Citazione:
A.M. Bester e B.H. Harvey, "Early suppression of striatal cyclic GMP may pre-determine the induction and severity of chronic haloperidol-induced vacous chewing movements", METAB BRAIN, 15(4), 2000, pp. 275-285

Abstract

Haloperidol persists in brain tissue long after discontinuation while haloperidol -induced tardive dyskinesia often worsens after withdrawal of the drug. The mechanism of haloperidol -associated tardive dyskinesia is unknown, although neurotoxic pathways are suspected. Nitric oxide (NO) synthase (NOS) inhibitors exacerbate haloperidol -induced catalepsy, while haloperidolitself is a potent neuronal NOS inhibitor in vitro. Since NO and cGMP are involved in striatal neural plasticity, this study investigates a possible relation between cGMP and extrapyramidal symptoms as early predictors of haloperidol associated tardive dyskinesia. Sprague-Dawley rats were administered either water or oral haloperidol (0.25mg/kg/d po) for 17 weeks, followed by 3 weeks withdrawal. Saline (ip) or the nNOS/guanylate cyclase inhibitor, methylene blue (5mg/kg/d ip), were coadministered with haloperidol for the first three weeks of treatment. Vacous chewing movements (VCM's) were continuously monitored, followed by the determination of striatal cGMP and peripheral serum nitrogen oxide (NOx) levels. Chronic haloperidol engendered significant VCM's, with acute withdrawal associated with significantly reduced striatal cGMP levels as well as reduced serum NOx. Furthermore, suppressed cGMP levels were maintained and VCM's were significantly worse after early administration of methylene blue to the chronic haloperidol group. However, serum NOx was unchanged from control. We conclude that the central effects of chronic haloperidol on striatal NO-cGMP function persist for up to 3 weeks post-withdrawal. Moreover, suppression of striatal cGMP constitutesan early neuronal insult that determines the presence and intensity of haloperidol -associated motor dysfunction.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 18/01/20 alle ore 08:14:43