Large, daily voluntary intakes of benzodiazepine (BZ) solutions will be produced in rats by the technique of schedule-induced overindulgence. The elevated drug solution ingestion levels for flurazepam and chlordiazepoxide will be compared with vehicle (water) ingestion over a range of inducing conditions both in fluid acceptance and preference situations. Results will be related to blood drug and metabolite levels and to similar ingestion arrangements with etonitazene. Physical dependence on BZ's will be evaluated: (1) both by withdrawal and by precipitation with BZ antagonists with audiogenic triggering, and (2) by changes in a discriminative fine motor control performance in separate experiments. The motor studies involve a force-transducer-holding steadiness test and will also explore the acute, chronic, withdrawal and precipitated withdrawal from flurazepam and diazepam. A number of anxiolytic and putative anxiolytic agents will be evaluated by an NaCl solution ingestion procedure. Median effective doses will be determined for phenobarbital, diazepam, oxazepam, trifluoperizine, reserpine, PCP, zopiclone, Ro 5-4864, clobazam and tracazolate in order to develop a testing procedure for anxiolytic activity in addition to the standard conflict tests.
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