ArticlesDiscriminative Stimulus Effects of Drugs Acting at GABAA Receptors: Differential Profiles and Receptor Selectivity
Section snippets
Stimulus effects of benzodiazepines and related drugs
Experimental animals including rats, pigeons, rhesus monkeys, and baboons readily learn to discriminate benzodiazepines from placebo. The stimulus effects of this group of drugs have been analyzed in great detail following early studies using chlordiazepoxide (3) and diazepam (9). In general, there is complete cross-substitution between different benzodiazepines, and the potencies of different drugs to substitute for diazepam were found to correlate highly with their in vitro affinities to bind
Chlordiazepoxide cue in rats
Rats were trained to discriminate a dose of 5 mg/kg of chlordiazepoxide from saline using a standard fixed-ratio (FR)10 food reinforcement schedule during daily 15 min sessions [see (20) for more details of the procedure]. The discrimination was rapidly learned, and the chlordiazepoxide ED50 doses for drug lever choice and decreases in rates of responding were approximately 2 and 12 mg/kg, respectively (values differed only slightly for a number of experiments carried out during a period of
Conclusions
Experimental animals can be trained to discriminate compounds acting at a variety of sites on the GABAA receptor complex. This method, therefore, has considerable potential for allowing a fine analysis of the pharmacology of drugs that potentiate or inhibit GABAergic neurotransmission. Although the discriminative stimulus effects of compounds acting at BZ(ω) binding sites have been investigated in some depth, a number of questions deserve further study. These include the significance of BZ(ω)
Acknowledgements
This article was presented at the Meeting “Drug Discrimination in Behavioural Neuroscience,” Beerse (Antwerp), August 30–September 1, 1998.
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2011, European Journal of PharmacologyCitation Excerpt :Drug discrimination has proven to constitute a valuable method to investigate in vivo mechanisms of action for non-selective classical benzodiazepines (Lelas et al., 2000). Using drug discrimination, compounds with apparent selectivity for α1-containing GABAA receptors could be discerned from those also acting on non-α1-containing GABAA receptors (Sanger et al., 1999). Recently, Mirza and colleagues specifically trained rats on the non-selective classical benzodiazepine chlordiazepoxide (CDP) and the α1-selective GABAA receptor positive allosteric modulator (PAM) zolpidem in a two-lever operant procedure (Mirza et al., 2006).
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2007, Haddad and Winchester's Clinical Management of Poisoning and Drug Overdose, Fourth EditionEffects of chlordiazepoxide on the emotional reactivity and motor capacities in the cerebellar Lurcher mutant mice
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