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Functional Changes in Rat Nigral GABA A Receptors Induced by Degeneration of the Striatonigral GABAergic Pathway: An Electrophysiological Study of Receptors Incorporated into Xenopus Oocytes

Sanna, Enrico ; Motzo, Costantino ; Usala, Marcello ; Pau, Davide ; Cagetti, Elisabetta ; Biggio, Giovanni

Journal of Neurochemistry, June 1998, Vol.70(6), pp.2539-2544 [Rivista Peer Reviewed]

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  • Titolo:
    Functional Changes in Rat Nigral GABA A Receptors Induced by Degeneration of the Striatonigral GABAergic Pathway: An Electrophysiological Study of Receptors Incorporated into Xenopus Oocytes
  • Autore: Sanna, Enrico ; Motzo, Costantino ; Usala, Marcello ; Pau, Davide ; Cagetti, Elisabetta ; Biggio, Giovanni
  • Descrizione: Expression of rat brain γ‐aminobutyric acid type A (GABA) receptors in oocytes can be achieved by injection of the oocytes with synaptosomes. This approach has now been applied to evaluate changes in the function of nigral GABA receptors after degeneration of the striatonigral GABAergic pathway induced by the unilateral infusion of kainic acid into the rat striatum. Ten days after striatal injection, synaptosomal membranes were prepared from the substantia nigra and introduced into oocytes. Nigral GABA receptors incorporated into the oocyte cell membrane were then characterized electrophysiologically under voltage‐clamp conditions. The maximal amplitude of GABA‐induced Cl currents in oocytes injected with synaptosomes from denervated substantia nigra was twice that observed in oocytes injected with synaptosomes from control substantia nigra. The concentration of GABA required for the half‐maximal response did not differ between the two groups of oocytes. In addition, the potentiation of GABA‐induced currents by the benzodiazepine diazepam (1 µ) and the steroid derivative allopregnanolone (3 µ) was increased by ∼65 and 60%, respectively, in oocytes injected with synaptosomes from denervated substantia nigra compared with those injected with control synaptosomes. The concentrations of diazepam and allopregnanolone giving half‐maximal responses were not affected by denervation. In contrast, the inhibitory effects of the benzodiazepine receptor inverse agonists FG 7142 (10 µ) and 6,7‐dimethoxy‐4‐ethyl‐β‐carboline‐3‐carboxylic acid ethyl ester (1 µ) were reduced by 48 and 38%, respectively, after denervation. These results indicate that the up‐regulation of nigral GABA receptors induced by degeneration of the striatonigral GABAergic pathway is associated with an increased efficacy of positive allosteric modulators, such as benzodiazepines and steroids, and with a reduced efficacy of negative allosteric modulators such as β‐carbolines.
  • Fa parte di: Journal of Neurochemistry, June 1998, Vol.70(6), pp.2539-2544
  • Soggetti: Substantia Nigra ; Gabaergic Denervation ; Gaba Receptors ; Diazepam ; Allopregnanolone ; Oocytes
  • Identificativo: ISSN: 0022-3042 ; E-ISSN: 1471-4159 ; DOI: 10.1046/j.1471-4159.1998.70062539.x

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