Abstract
The sedative, anxiolytic, and amnesic effects of diazepam were compared to those of CL 218,872, a triazolopyridazine that has a preferential affinity for the benzodiazepine ω1 receptor subtype. Spontaneous locomotion was assessed using a running wheel, anxiety was assessed using an open-field divided into central and peripheral areas (thigmotaxis), and amnesia was assessed using the Morris water maze. It was found that CL 218,872, like diazepam, depressed spontaneous locomotion, reduced anxiety, and impaired place learning in a dose-dependent manner. Flumazenil, a benzodiazepine receptor antagonist with a similar affinity for both ω1 and ω2 subtypes, reversed all of the effects of diazepam and antagonized the anxiolytic and amnesic effects, and some but not all of the sedative effects of CL 218,872. These results suggest that the selective activation of the ω1 receptor subtype by CL 218,872 is sufficient to produce sedation, anxiolysis, and amnesia in a manner similar to that produced by the coactivation of both the ω1 and ω2 receptor subtypes with diazepam.
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McNamara, R.K., Skelton, R.W. Like diazepam, CL 218,872, a selective ligand for the benzodiazepine ω1 receptor subtype, impairs place learning in the Morris water maze. Psychopharmacology 107, 347–351 (1992). https://doi.org/10.1007/BF02245160
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DOI: https://doi.org/10.1007/BF02245160