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Titolo:
Antipsychoticlike effects of amoxapine, without catalepsy, using the prepulse inhibition of the acoustic startle reflex test in rats
Autore:
Wadenberg, MLG; Sills, TL; Fletcher, PJ; Kapur, S;
Indirizzi:
Ctr Addict & Mental Hlth, Sect Biopsychol, Toronto, ON M5T 1R8, Canada CtrAddict & Mental Hlth Toronto ON Canada M5T 1R8 to, ON M5T 1R8, Canada Univ Toronto, Ctr Addict & Mental Hlth, Toronto, ON, Canada Univ Toronto Toronto ON Canada Addict & Mental Hlth, Toronto, ON, Canada Univ Toronto, Dept Psychiat, Toronto, ON, Canada Univ Toronto Toronto ON Canada ronto, Dept Psychiat, Toronto, ON, Canada Univ Toronto, Dept Psychol, Toronto, ON, Canada Univ Toronto Toronto ON Canada oronto, Dept Psychol, Toronto, ON, Canada
Titolo Testata:
BIOLOGICAL PSYCHIATRY
fascicolo: 7, volume: 47, anno: 2000,
pagine: 670 - 676
SICI:
0006-3223(20000401)47:7<670:AEOAWC>2.0.ZU;2-5
Fonte:
ISI
Lingua:
ENG
Soggetto:
RECEPTOR ANTAGONIST; DOPAMINE; CLOZAPINE; DRUGS; SCHIZOPHRENIA; 5-HT2A; MDL-100,907; ENHANCEMENT; MECHANISMS; DISRUPTION;
Keywords:
dopamine receptors; serotonin receptors; prepulse inhibition of the acoustic startle reflex; catalepsy; atypical antipsychotics; rat;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
32
Recensione:
Indirizzi per estratti:
Indirizzo: Wadenberg, MLG Ctr Addict & Mental Hlth, Sect Biopsychol, 250 Coll St, Toronto, ON M5T 1R8, Canada Ctr Addict & Mental Hlth 250 Coll St Toronto ON Canada M5T 1R8
Citazione:
M.L.G. Wadenberg et al., "Antipsychoticlike effects of amoxapine, without catalepsy, using the prepulse inhibition of the acoustic startle reflex test in rats", BIOL PSYCHI, 47(7), 2000, pp. 670-676

Abstract

Background: The dibenzoxazepine amoxapine was introduced as art antidepressant but has shown antipsychotic-like activity ill a number of animal screening tests. A recent positron emission tomography study showed a 5-HT2/D-2,receptor occupancy profile of amoxapine that is very similar to that of established atypical antipsychotics. Schizophrenics display) deficits in sensory gating mechanisms, such? as prepulse inhibition (PPI) of the acoustic startle reflex.. A similar deficit can be produced by dopamine (DA) and by 5-HT2A/C receptor agonists in rats, Antipsychotic compounds revel-se this effect. Methods: Effects of amoxapine on apomorphine- or 1-(2,5-dirmethoxy-4-iodophenyl)-2-aminopropane (DOI)- induced disruption of PPI were studied in adult male Sprague-Dawley mrs, The extrapyramidal side effect (EPS) liability of amoxapine was assessed using the inclined grid catalepsy (CAT) test. Statistical analyses were performed by analysis of variance (ANOVA) for fully repeated measures (PPI) and by the Kruskal-Wallis one-way ANOVA by ranks (CAT). Results: Apomorphine (0.5 mg/kg) produced a significant reduction in PPI compared with the case of rats in the saline control group. Pretreatment with amoxapine (10 mg/kg) significantly attenuated the apomorphine-induced disruption of PPI. DOI (0.5 mg/kg) significantly reduced PPI compared with saline controls. Pretreatment with amoxapine (5 or 10 mg/kg produced a significant attenuation of the DOI-induced disruption of PPI. Amoxapine by itself did not alter PPI. Amoxapine (5 or 10 mg/kg) did not produce CAT. Conclusions: The DA D-2/5-HT2 receptor antagonist amoxapine produced an antipsychoticlike reversal of both apomorphine- and DOI-induced disruption ofPPI. Furthermore, the same doses of amoxapine that reversed disruption of PPI did not produce CAT. The results confirm and lend further support to the results of previous studies on amoxapine, suggesting that amoxapine mightpossess antipsychotic activity with little propensity for producing EPS. (C) 2000 Society of Biological Psychiatry.

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Documento generato il 18/01/20 alle ore 10:37:27