Ambien online research references
Alcohol Alcohol Suppl. 1994;2:89-95.
GABAA and NMDA receptor subunit mRNA expression in ethanol dependent rats.
Morrow AL, Devaud LL, Bucci D, Smith FD.
Center for Alcohol Studies, University of North Carolina School of Medicine, Chapel Hill 27599-7178, USA.
Recent studies have shown that alterations in gamma-aminobutyric acid (GABAA) and N-methyl-D-aspartate (NMDA) receptor subunit mRNA levels are associated with the effects of chronic ethanol exposure as well as genetic selection for ethanol withdrawal seizure sensitivity. We have previously shown that chronic ethanol exposure in rats results in a decrease in the levels of GABAA receptor alpha 1 and alpha 2 subunit mRNAs in cerebral cortex, an increase in the levels of alpha 6 subunit mRNAs in cerebellum and no alteration in alpha 3, GAD, ribosomal RNA or polyA + RNA levels in these regions. Since chronic ethanol administration increases the expression of [3H]Ro15-4513 binding sites in cortex and cerebellum with no effect on other GABAA receptor recognition sites, we hypothesized that the expression of other subunits would be altered in these regions. In addition, since ethanol appears to interact with zolpidem-sensitive GABAA receptors in rat brain, we investigated the effect of chronic ethanol administration on these recognition sites. Chronic ethanol administration increased [3H]zolpidem binding with no effect on levels of GABAA receptor beta 2 and gamma 2 subunit mRNAs. In addition, we examined the levels of NMDAR1 receptor subunit mRNAs since chronic ethanol administration results in increased levels of [3H]MK-801 recognition sites on NMDA receptors. NMDAR1 receptor subunit mRNAs were not altered following chronic ethanol exposure in rat cortex or hippocampus. These studies underscore the specificity of ethanol interactions with these receptors and the importance of understanding the mechanisms of both GABAA and NMDA receptor regulation in elucidating the etiology of ethanol dependence.
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J Pharmacol Exp Ther. 1997 Jan;280(1):162-73.
Discriminative stimulus effects of zolpidem in pentobarbital-trained subjects: I. Comparison with triazolam in rhesus monkeys and rats.
Rowlett JK, Woolverton WL.
Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson, USA.
The present study compared the discriminative stimulus effects of the imidazopyridine, zolpidem, with a triazolobenzodiazepine, triazolam, in pentobarbital-trained rhesus monkeys and rats. Rhesus monkeys (n = 4), trained to discriminate pentobarbital (10 mg/kg intragastric [i.g.]) from saline under a FR 1 discrete-trials shock avoidance procedure, were given zolpidem (0.10-30 mg/kg i.g.) or triazolam (0.01-0.3 mg/kg i.g.). Both zolpidem and triazolam produced dose-dependent increases in pentobarbital-appropriate responding that reached 80% or greater at the highest doses tested. Zolpidem, but not triazolam, increased latency to respond in a dose-dependent manner. Sprague-Dawley rats (n = 12), trained to discriminate pentobarbital (8.0 mg/kg i.p.) from saline under a FR 10 schedule of food reinforcement, were given zolpidem (0.50-4.0 mg/kg i.p.; 5-, 15- and 45-min pretreatment) or triazolam (0.025-0.20 mg/kg i.p., 15-min pretreatment). Zolpidem occasioned intermediate drug-appropriate responding (maximum group mean = 48%) at the 5- and 15-min pretreatment times and no drug-appropriate responding at the 45-min pretreatment time. In contrast, triazolam occasioned > or = 80% pentobarbital-appropriate responding at 0.10 and 0.20 mg/kg. Both zolpidem and triazolam produced dose-dependent decreases in the rate of responding. The rate-decreasing effects of zolpidem were maximal at the 5-min pretreatment time and had dissipated after the 45-min pretreatment time. Further studies were conducted in rats to equate procedural variables between the monkey and rat studies. When the FR was reduced from 10 to 1, zolpidem occasioned 26 to 62% pentobarbital-appropriate responding over a dose range of 1.0 to 6.0 mg/kg i.p. After i.g. administration, zolpidem occasioned 100% drug-appropriate responding at the highest dose tested (6.0 mg/kg); however, only two of seven rats responded. Taken together, these data raise the possibility of a species difference between non-human primates and rats in the pentobarbital-like discriminative stimulus effects of zolpidem.
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Eur Neuropsychopharmacol. 1995 Dec;5(4):523-6.
Behavioural responsiveness to picrotoxin and desipramine in adult rats prenatally exposed to different benzodiazepine receptor agonists.
Cannizzaro C, Cannizzaro E, Gagliano M, Mangiapane N.
Institute of Pharmacology, University of Palermo, Italy.
The behavioural responsiveness to picrotoxin and desipramine was investigated in adult rats prenatally exposed to different benzodiazepine receptor agonists such as diazepam, alprazolam and zolpidem. Prenatal exposure to diazepam and alprazolam similarly potentiated the anti-immobility effect on the forced swimming test and the inhibitory effect on spontaneous motor activity of picrotoxin and desipramine and increased the seizure sensitivity to picrotoxin. Prenatal zolpidem seems to be ineffective. These data suggest that, despite the differences in their pharmacodynamic profile, prenatal exposure to diazepam and alprazolam, but not zolpidem, may have similar permanent consequences on the behavioural effects of drugs acting on the GABAA receptors.
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Receptors Channels. 1996;4(3):179-95.
Effect of subunit composition on GABAA receptor complex characteristics in a baculovirus expression system.
Hartnett C, Brown MS, Yu J, Primus RJ, Meyyappan M, White G, Stirling VB, Tallman JF, Ramabhadran TV, Gallager DW.
Neurogen Corporation, Dept. of Molecular Biology, Branford, CT 06405, USA.
A baculovirus expression system was used to produce functional human recombinant GABAA receptors in Sf-9 insect cells in order to study the biochemistry, pharmacology and functional characteristics of this receptor complex. We have identified and characterized various factors which influence the level of receptor expression in multiple virus infections. We have shown that the level of expression of the GABAA receptor complex varies with the levels of expression of the individual subunits. We have also shown that the assembly process has a defined timecourse, and it is dependent upon the ratio of the number of infectious virus particles (MOI ratio) of each subunit in multi-virus infections. In multiple infections, the capacity for expression of the infected cell is shared proportionally by entering virus particles and, there is a direct correlation between the amounts of subunit mRNA and levels of subunit protein expression, and the amount of ligand binding to expressed protein. Finally, reinfection of previously infected cells does not result in subsequent protein expression. Knowledge of these various factors allows us to construct recombinant GABAA receptor complexes with reproducibility and flexibility with regard to subunit composition. By co-expression of alpha, beta, and gamma subunits, both the recognition site for GABA and the allosteric (benzodiazepine) modulatory site are formed and appear to reproduce the pharmacology of endogenously expressed receptors as measured in mammalian CNS. Only a single receptor is produced irrespective of the expression levels of the subunits, showing that GABAA receptor assembly is highly regulated.
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Nucl Med Biol. 1999 Oct;26(7):743-8.
Evaluation of [methyl-3H]L655,708 and [ethyl-3H]RY80 as putative PET ligands for central GABA(A) receptors containing alpha5 subunit.
Opacka-Juffry J, Hirani E, Dawson GR, Luthra SK, Hume SP.
MRC Cyclotron Unit, Hammersmlith Hospital, London, UK. jolanta
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