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Titolo:
5-HT MODULATION OF AUDITORY AND VISUAL SENSORIMOTOR GATING .1. EFFECTS OF 5-HT RELEASERS ON SOUND AND LIGHT PREPULSE INHIBITION IN WISTAR RATS
Autore:
KEHNE JH; PADICH RA; MCCLOSKEY TC; TAYLOR VL; SCHMIDT CJ;
Indirizzi:
HOECHST MARION ROUSSEL INC,2110 E GALBRAITH RD CINCINNATI OH 45215
Titolo Testata:
Psychopharmacology
fascicolo: 1-2, volume: 124, anno: 1996,
pagine: 95 - 106
Fonte:
ISI
Lingua:
ENG
Soggetto:
ACOUSTIC STARTLE REFLEX; 3,4-METHYLENEDIOXYMETHAMPHETAMINE MDMA; PARA-CHLOROAMPHETAMINE; ANTIPSYCHOTIC-DRUGS; RECEPTOR ANTAGONIST; DOPAMINE RELEASE; FENFLURAMINE; SEROTONIN; MICRODIALYSIS; AGONISTS;
Keywords:
PREPULSE INHIBITION; SENSORIMOTOR GATING; SCHIZOPHRENIA; WISTAR RATS; SEROTONIN; P-CHLOROAMPHETAMINE, PCA; 3,4-METHYLENEDIOXYMETHAMPHETAMINE, MDMA; N-ETHYL-3,4-METHYLENEDIOXYMETHAMPHETAMINE, MDEA; FENFLURAMINE; CLONIDINE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Physical, Chemical & Earth Sciences
Physical, Chemical & Earth Sciences
Physical, Chemical & Earth Sciences
Science Citation Index Expanded
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
59
Recensione:
Indirizzi per estratti:
Citazione:
J.H. Kehne et al., "5-HT MODULATION OF AUDITORY AND VISUAL SENSORIMOTOR GATING .1. EFFECTS OF 5-HT RELEASERS ON SOUND AND LIGHT PREPULSE INHIBITION IN WISTAR RATS", Psychopharmacology, 124(1-2), 1996, pp. 95-106

Abstract

Increasing evidence suggests an important role for serotonin (5-HT) neuron in the etiology and treatment of schizophrenia. The prepulse inhibition paradigm is used as a model for sensorimotor gating processes that are disrupted in schizophrenia. The present study assessed the general role of 5-HT in modulating auditory and visual prepulse inhibition in Wistar rats. A general overactivation of central serotonerigic pathways was produced pharmacologically by four different agents which all shared the common property of releasing 5-HT, i.e., p-chloroamphetamine, 3,4-methylenedioxymethamphetamine, N-ethyl-3,4-methylenedioxymethamphetamine, or fenfluramine. Within each test session, both sound and light prepulses were sued to obtain a cross-modal assessment of auditory and visual sensory gating processes. All four 5-HT releasing agents produced dose-related disruptions of auditory and visual prepulse inhibition, with p-chloroamphetamine being the most potent. The releasers depressed baseline to varying degrees. The alpha(2)-adrenergic agonist clonidine decreased baseline startle without substantially disrupting prepulse inhibition, demonstrating that the two effects were dissociable. Using fenfluramine as the most selective 5-HT releaser, two approaches were used to demonstrate 5-HT mediation of its disruptive effect on prepulse inhibition. In the first approach, the selective 5-HTuptake blocker MDL 28,618A was used to prevent fenfluramine-induced 5-HT release. In the second approach, prior exposure to a neurotoxic dose of p-chloroamphetamine (10 mg/kg) was used to produce a substantial, sustained depletion of cortical 5-HT, presumably reflecting the lossof 5-HT terminals. Both approaches reduced the disruptive effect of fenfluramine on auditory and visual prepulse inhibition, thereby demonstrating 5-HT mediation of these effects. Neither manipulation significantly affected the depressant effect of fenfluramine on startle baseline, demonstrating that the baseline-reducing and prepulse inhibition-reducing effects of fenfluramine could be dissociated. MDL 28,618A alone did not affect prepulse inhibition or basal startle levels, demonstrating an important functional difference between pharmacologically induced 5-HT uptake blockade and 5-HT release. In summary, these data indicate that serotonergic overactivation can disrupt auditory and visualsensorimotor gating as measured using sound and light prepulse inhibition in rats. These data support a potential role of excessive 5-HT activity as a contributing factor to disrupted sensory gating processes seen in schizophrenia and possibly other neuropsychiatric disorders.

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Documento generato il 19/01/20 alle ore 09:08:05