LACK OF TOLERANCE TO THE ANXIOLYTIC EFFECT OF DIAZEPAM AND PENTOBARBITAL FOLLOWING CHRONIC ADMINISTRATION IN PERINATALLY UNDERNOURISHED RATS

Adult female rats, undernourished at perinatal age, were evaluated for anxiolytic action in the plus-maze test after acute and chronic admin istration of diazepam (DZP) and pentobarbital (PTB), Deprived (D) rats chronically treated with vehicle showed an increased anxiety as compa red with control (C) animals. A single intraperitoneal (i.p.) administ ration of DZP (1 mg/kg) or PTB (7.5 mg/kg) produced similar anticonfli ct effect in both C and D rats. Tolerance to the anxiolytic effect of DZP and PET developed in C rats after a 15-day administration schedule , whereas no tolerance was observed in D animals. Drug disposition was not altered after chronic treatment either in C or in D rats. gamma-a minobutyric acid (GABA)-mediated chloride uptake in microsacs of cereb ral cortex of naive D rats was decreased as compared with naive C rats . After chronic DZP administration (1 mg/kg/day i.p. for 15 days), GAB A-mediated Cl-36(-) influx in brain cortex microsacs of C rats did not change; however, GABA efficacy was increased in microsacs of D animal s. In addition, chronic DZP treatment induced GABA-benzodiazepine unco upling in brain cortex of C rats, but not in D animals, as assessed by chloride uptake in microsacs, Chronic PTB treatment (7.5 or 30 mg/kg/ day i,p, for 15 days) did not modify GABA stimulation or GABA-PTB inte raction in cortical microsacs of C or D rats. (C) 1998 Elsevier Scienc e Inc.