Naslov
The effect of prolonged zolpidem treatment on GABA-A receptors in primary culture of rat cerebellar granule neurons

Autori
Vlainić (Lazić), Josipa ; Peričić, Danka

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Abstracts of the 9th International Congress of Polish Neuroscience Society and The 1st FENS featured Regional Meeting ; u: Acta Neurobiologiae Experimentalis 69 (2009) (3) / Krzystof Turlejski - Varšava, 2009, 302-302

Skup
International Congress of Polish Neuroscience Society (9 ; 2009) ; FENS featured Regional Meeting (1 ; 2009)

Mjesto i datum
Varšava, Poljska, 09.09.2009. - 12.09.2009

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
zolpidem; GABA-A receptors; cerebellar neurons

Sažetak
The aim of this study was to further explore the mechanisms leading to adaptive changes in GABA-A receptors following their prolonged exposure to hypnotic zolpidem, a positive allosteric modulator of GABA-A receptors. Imidazopyridine zolpidem is the most widely prescribed non-benzodiazepine hypnotic, with preferential, although not exclusive, binding for receptors containing alpha1 subunit. It was suggested that drugs with high selectivity for alpha1 containing receptors produce upon repeated treatment less tolerance and dependence than classical benzodiazepines. As an extension of our previous work, we treated cerebellar neuronal cells isolated from 8-days old rats with 10 microM zolpidem during 48 h. Radioligand binding studies and RT-PCR analysis were preformed under conditions previously described (Pericic et al., Naunyn-Schmiedeberg s Arch. Pharmacol. 375: 177-187, 2007). Results demonstrate that prolonged treatment of these cells with zolpidem induced changes neither in GABA-A receptor number nor in expression of alpha1 subunit mRNA. As evidenced by a decreased ability of GABA to stimulate [3H]flunitrazepam binding, chronic exposure of these cells to zolpidem produced the functional uncoupling between GABA and benzodiazepine binding sites on GABA-A receptor complex. If this mechanism is responsible for the development of tolerance following chronic administration of classic benzodiazepines, than one might expect that chronic zolpidem might also induce tolerance.

Izvorni jezik
Engleski

POVEZANOST RADA