Discriminative stimulus effects of drugs acting at GABA(A) receptors: Differential profiles and receptor selectivity

The GABA(A) receptor complex contains a number of binding sites at which a variety of psychotropic drugs, including benzodiazepines, barbiturates, and some neurosteroids, act to potentiate or inhibit the effect of the transmi tter. Many studies have reported that these drugs can produce discriminativ e stimulus actions, but the cueing effects of compounds acting at different sites to enhance the effects of GABA are not identical. The discriminative stimulus effects of benzodiazepines have been analyzed in detail, and ther e is also a great deal of information available on the effects of non-benzo diazepine compounds acting at BZ(omega) recognition sites, which form part of the GABAA receptor complex. Of particular interest are compounds with se lectivity for the BZ(1)(omega(1)) receptor subtype including zolpidem, zale plon, and C1 218,872. BZ(1)(omega(1))-selective drugs substitute for the di scriminative stimulus produced by chlordiazepoxide only partially and at se dative doses. This is consistent with the view that sedative effects of BZ( omega) receptor agonists are mediated by the BZ(1)(omega(1)) receptor subty pe, whereas the discriminative stimulus produced by chlordiazepoxide may be produced by activity at the BZ(2)(omega(2)) subtype. Analysis of this hypo thesis is complicated by the variety of levels of intrinsic activity shown by different drugs. (C) 1999 Elsevier Science Inc.