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Titolo:
GABA(A) receptors containing alpha 5 subunits in the CA1 and CA3 hippocampal fields regulate ethanol-motivated behaviors: An extended ethanol reward circuitry
Autore:
June, HL; Harvey, SC; Foster, KL; McKay, PF; Cummings, R; Garcia, M; Mason, D; Grey, C; McCane, S; Williams, LS; Johnson, TB; He, XH; Rock, S; Cook, JM;
Indirizzi:
Indiana Univ Purdue Univ, Dept Psychol, Psychobiol Program, Indianapolis, IN 46202 USA Indiana Univ Purdue Univ Indianapolis IN USA 46202 anapolis, IN 46202 USA Eli Lilly & Co, Neurosci Lab, Indianapolis, IN 46285 USA Eli Lilly & Co Indianapolis IN USA 46285 Lab, Indianapolis, IN 46285 USA Univ Wisconsin, Dept Chem, Milwaukee, WI 53201 USA Univ Wisconsin Milwaukee WI USA 53201 Dept Chem, Milwaukee, WI 53201 USA
Titolo Testata:
JOURNAL OF NEUROSCIENCE
fascicolo: 6, volume: 21, anno: 2001,
pagine: 2166 - 2177
SICI:
0270-6474(20010315)21:6<2166:GRCA5S>2.0.ZU;2-#
Fonte:
ISI
Lingua:
ENG
Soggetto:
INSENSITIVE BENZODIAZEPINE RECEPTORS; VENTRAL TEGMENTAL AREA; RAT-BRAIN; NUCLEUS-ACCUMBENS; HIGH-AFFINITY; PREFRONTAL CORTEX; ALCOHOL-DRINKING; WISTAR RATS; ANTAGONIST; PHARMACOLOGY;
Keywords:
ethanol; GABA; alpha 5 subunit; reinforcement; hippocampus; alcohol-preferring (P) rat;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
67
Recensione:
Indirizzi per estratti:
Indirizzo: June, HL Indiana Univ Purdue Univ, Dept Psychol, Psychobiol Program, LD 124,402 N Blackford St, Indianapolis, IN 46202 USA Indiana Univ Purdue Univ LD 124,402 N Blackford St Indianapolis IN USA 46202
Citazione:
H.L. June et al., "GABA(A) receptors containing alpha 5 subunits in the CA1 and CA3 hippocampal fields regulate ethanol-motivated behaviors: An extended ethanol reward circuitry", J NEUROSC, 21(6), 2001, pp. 2166-2177

Abstract

GABA receptors within the mesolimbic circuitry have been proposed to play a role in regulating alcohol-seeking behaviors in the alcohol-preferring (P) rat. However, the precise GABA(A) receptor subunit(s) mediating the reinforcing properties of EtOH remains unknown. We examined the capacity of intrahippocampal infusions of an alpha5 subunit-selective (similar to 75-fold) benzodiazepine (BDZ) inverse agonist [i.e., RY 023 (RY) (tert-butyl 8-(trimethylsilyl) acetylene-5,6-dihydro-5-methyl-6-oxo-4H-imidazo [1,5a] [1,4] benzodiazepine-3-carboxylate)] to alter lever pressing maintained by concurrent presentation of EtOH (10% v/v) and a saccharin solution (0.05% w/v). Bilateral (1.5-20 mug) and unilateral (0.01-40 mug) RY dose-dependently reduced EtOH-maintained responding, with saccharin-maintained responding being reduced only with the highest doses (e.g., 20 and 40 mug). The competitive BDZ antagonist ZK 93426 (ZK) (7 mug) reversed the RY-induced suppression on EtOH-maintained responding, confirming that the effect was mediated via the BDZ site on the GABA(A) receptor complex. Intrahippocampal modulation of the EtOH-maintained responding was site-specific; no antagonism by RY after intra-accumbens [nucleus accumbens (NACC)] and intraventral tegmental [ventral tegmental area (VTA)] infusions was observed. Because the VTA and NACC contain very high densities of alpha1 and alpha2 subunits, respectively, we determined whether RY exhibited a "negative" or "neutral" pharmacological profile at recombinant alpha1 beta3 gamma2, alpha2 beta3 gamma2, and alpha5 beta3 gamma2 receptors expressed in Xenopus oocytes. RY produced "classic" inverse agonism at all alpha receptor subtypes; thus, a neutral efficacy was not sufficient to explain the failure of RY to alter EtOH responding in the NACC or VTA. The results provide the first demonstration that the alpha5-containing GABA(A) receptors in the hippocampus play an important role in regulating EtOH-seeking behaviors.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 27/01/20 alle ore 01:28:56