Effect of age on benzodiazepine-induced behavioural convulsions in rats

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Abstract
The benzodiazepines are a class of drugs used to alleviate anxiety. As such they constitute one of the most commonly prescribed compounds, due in part to their efficacy and safety. The physiological effect of these drugs is probably through interactions with a low affinity benzodiazepine binding site and two (types 1 and 2) higher affinity sites. The ontogenesis of these latter two binding sites in the rat differs, with the type 2 binding site being predominant at birth and the type 1 binding site increasing in number after the second week after birth. The differential development of these two receptor types is important because the immature organism may have different physiological and behavioural responses from the adult. Here we demonstrate an important difference: that a prototypic benzodiazepine, chlordiazepoxide, and a water-soluble benzodiazepine, flurazepam, produce behavioural convulsions in the preweanling rat. The convulsions are antagonized by the benzodiazepine blocker Ro-15-1788. The triazolopyridizine CL-218872, specific to the type 1 receptor, does not share this action. We suggest that this paradoxical convulsant effect of chlordiazepoxide and flurazepam is due to activation of the type 2 receptor in the absence of the type 1 receptor in the immature rat.