1. Dear Drugs-Forum readers: We are a small non-profit that runs one of the most read drug information & addiction help websites in the world. We serve over 4 million readers per month, and have costs like all popular websites: servers, hosting, licenses and software. To protect our independence we do not run ads. We take no government funds. We run on donations which average $25. If everyone reading this would donate $5 then this fund raiser would be done in an hour. If Drugs-Forum is useful to you, take one minute to keep it online another year by donating whatever you can today. Donations are currently not sufficient to pay our bills and keep the site up. Your help is most welcome. Thank you.
    PLEASE HELP

Different GABAA receptor subtypes mediate the anxiolytic, abuse-related, and motor effects of benzod

Different GABAA receptor subtypes mediate the anxiolytic, abuse-related, and motor effects of benzod

  1. Jatelka
    Proceedings of the National Academy of Sciences of the USA 2005 Jan 18;102(3):915-20

    Rowlett JK (http://www.ncbi.nlm.nih.gov/sites/e...l.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus), Platt DM (http://www.ncbi.nlm.nih.gov/sites/e...l.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus), Lelas S (http://www.ncbi.nlm.nih.gov/sites/e...l.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus), Atack JR (http://www.ncbi.nlm.nih.gov/sites/e...l.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus), Dawson GR (http://www.ncbi.nlm.nih.gov/sites/e...l.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus).

    Benzodiazepines exert their effects by binding to multiple subtypes of the GABAA receptor, the predominant subtypes in the brain being those that contain alpha1-, alpha2-, alpha3-, and alpha5-subunits. To understand the potentially different roles of these subtypes in the therapeutic and side effects of benzodiazepines, we evaluated GABAA receptor subtype-preferring compounds in nonhuman primate models predictive of anxiolytic, sedative, motor, subjective, and reinforcing effects of benzodiazepine-type drugs. These compounds included zolpidem, which shows preferential binding to GABAA receptors containing alpha1-subunits (alpha1GABAA receptors); L-838,417, which shows functional selectivity for alpha2GABAA, alpha3GABAA, and alpha5GABAA receptors; and nonselective conventional benzodiazepines. The results provide evidence in nonhuman primates that alpha1GABAA receptors do not play a key role in the anxiolytic and muscle-relaxant properties of benzodiazepine-type drugs; instead, these effects involve alpha2GABAA, alpha3GABAA, and/or alpha5GABAA subtypes. Our results also suggest that the alpha1GABAA receptor subtype might be critically involved in the subjective, sedative, and motor effects of benzodiazepine-type drugs. In contrast, stimulation of alpha1GABAA receptors is sufficient, but not necessary, for mediation of the abuse potential of these drugs.