Neonatal damage to neocortex abolishes the anxiolytic action of diazepam in adult rats.

A neonatal cerebral cortical lesion was made in rats and the effects of diazepam on ultrasonic isolation calls in pups and footshock-elicited ultrasonic distress calls in young adult rats were assessed. There was no indication that the cortical lesion influenced the production of the ultrasonic distress calls in either pups or adults. Diazepam attenuated the ultrasonic isolation calls in all the pups with and without cortical lesion, and the distress calls in normal adult rats. However, diazepam failed to exert the effect in rats which received a neonatal cortical lesion. 8-Hydroxy-2-(di-n-propylamino)tetralin hydrobromide (8-OH-DPAT), another anxiolytic, was effective to diminish the distress calls even in the adult rats which had had the neonatal damage to the cortex. These findings indicate that the intact cerebral cortex is not always required for production of ultrasonic distress calls; however, the development of the neuronal mechanism involving benzodiazepine receptors to inhibit the ultrasonic expression of anxiety or fear in adult rats is dependent on the integrity of the cerebral cortex.