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Titolo:
HYPERSENSITIVITY TO SEROTONIN AND ITS AGONISTS IN SEROTONIN-HYPERINNERVATED NEOSTRIATUM AFTER NEONATAL DOPAMINE DENERVATION
Autore:
ELMANSARI M; RADJA F; FERRON A; READER TA; MOLINAHOLGADO E; DESCARRIES L;
Indirizzi:
MCGILL UNIV,DEPT PSYCHIAT,1033 AVE PINS OUEST MONTREAL H3A 1A1 PQ CANADA UNIV MONTREAL,FAC MED,DEPT PATHOL MONTREAL H3C 3J7 PQ CANADA UNIV MONTREAL,FAC MED,CTR RECH SCI NEUROL MONTREAL H3C 3J7 PQ CANADA UNIV MONTREAL,FAC MED,DEPT PHYSIOL MONTREAL H3C 3J7 PQ CANADA UNIV MONTREAL,FAC MED,DEPT PSYCHIAT MONTREAL H3C 3J7 PQ CANADA
Titolo Testata:
European journal of pharmacology
fascicolo: 1-2, volume: 261, anno: 1994,
pagine: 171 - 178
SICI:
0014-2999(1994)261:1-2<171:HTSAIA>2.0.ZU;2-V
Fonte:
ISI
Lingua:
ENG
Soggetto:
DEPLETING BRAIN-LESIONS; ADULT-RAT NEOSTRIATUM; INSITU HYBRIDIZATION HISTOCHEMISTRY; 6-HYDROXYDOPAMINE LESION; MESSENGER-RNA; NEURONAL RESPONSIVENESS; RECEPTORS; BINDING; 5-HT2; STRIATUM;
Keywords:
5-HT1B RECEPTOR; 5-HT2A RECEPTOR; 5-HT2C RECEPTOR; 6-HYDROXYDOPAMINE; MCPP (1-3-(M-CHLOROPHENYL)PIPERAZINE); DOI (1-(2,5-DIMETHOXY-4-IODOPHENYL)-2-AMINOPROPANE); IONTOPHORESIS; AUTORADIOGRAPHY;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
54
Recensione:
Indirizzi per estratti:
Citazione:
M. Elmansari et al., "HYPERSENSITIVITY TO SEROTONIN AND ITS AGONISTS IN SEROTONIN-HYPERINNERVATED NEOSTRIATUM AFTER NEONATAL DOPAMINE DENERVATION", European journal of pharmacology, 261(1-2), 1994, pp. 171-178

Abstract

Neonatal destruction of the nigrostriatal dopamine projection by intraventricular 6-hydroxydopamine leads to a serotonin (5-hydroxytryptamine, 5-HT) hyperinnervation of the adult neostriatum accompanied by increased radioligand binding to 5-HT1B, 5-HT1nonAB and 5-HT2 receptors. The consequences of such 5-HT receptor changes on neuronal responsiveness to 5-HT and corresponding receptor agonists were assessed with a quantitative iontophoretic approach. For comparative purposes, similar data were also obtained from rats 6-hydroxydopamine lesioned as adults, showing severe neostriatal dopamine denervation but no 5-HT hyperinnervation. In controls, 5-HT and its receptor agonists, m-chlorophenylpiperazine (mCPP; 5-HT1B/2C agonist) and dimethoxy-iodophenyl-aminopropane (DOI; 5-HT2A/2C agonist), depressed the firing rate of a majority of the units tested. Three months after neonatal 6-hydroxydopamine lesion (5-HT-hyperinnervated tissue), inhibitory responses to all three agents were significantly increased and comparable results were obtained for 5-HT and DOI in the rostral versus caudal neostriatum. After 6-hydroxydopamine lesion in adults, neither responsiveness to 5-HT, mCPP or DOI nor the density of 5-HT1B or 5-HT2A binding were significantly different from control. Thus, the up-regulation of 5-HT1B, 5-HT2A and possibly 5-HT2C receptors accompanying the 5-HT hyperinnervation afterneonatal but not after adult dopamine denervation was associated withincreased responsiveness (IT50) of neostriatal neurons to iontophoresed 5-HT and its receptor agonists. Under these conditions, neostriatal5-HT transmission might be enhanced in spite of a basal release seemingly comparable to normal (Jackson and Abercrombie, 1992, J. Neurochem. 58, 890). The elevated number of 5-HT2A receptors might also explainwhy systemic treatment with 5-HT2A receptor antagonists reverses the spontaneous hyperactivity observed in these rats (Luthman et al., 1991, J. Psychopharmacol. 5, 418).

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Documento generato il 30/03/20 alle ore 18:35:19