Neonatal cerebral cortical lesion abolishes the anxiolytic action of diazepam in adult rats: effects of location and extent of cortical lesion.
In our previous study, diazepam (DZP), a benzodiazepine receptor agonist, failed to suppress foot-shock-elicited ultrasonic vocalizations (USVs) in adult rats that had been neonatally lesioned in the neocortex. Because neonatal lesion of the neocortex did not influence the production of USVs, the presence of an anxiolytic mechanism of DZP is suggested apart from any anxiogenic mechanism in the brain. However, the previous study did not indicate any specific cortical regional lesions that impaired the normal development of the anxiolytic mechanism in the brain. The present study was undertaken in order to examine whether neonatal lesion of the neocortex, smaller and more localized than that in the previous study, abolishes the anxiolytic effect of DZP on foot-shock-elicited and air-puff-elicited USVs. A neonatal lesion about 2 mm diameter was made in the unilateral frontal cortex frontal to the hindlimb area or in the occipital cortex caudal to the hindlimb area. The attenuating effect of DZP on the USVs elicited by both aversive stimuli was found to be abolished only in the frontal cortex-lesioned rats. This finding indicates that the frontal cortex is likely to be specifically involved in the normal development of the benzodiazepine-anxiolytic mechanism in the brain.
Nakamura
Amane
A
Department of Neurophysiology, School of Veterinary Medicine, Azabu University, Fuchinobe, Sagamihara, Japan.
Naito
Hiroyuki
H
Inoue
Maki
M
Masaoka
Toshio
T
D000388:Air; D000818:Animals; D000831:Animals, Newborn; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001007:Anxiety / Q000188:drug therapy* / Q000517:prevention & control; D001930:Brain Injuries / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D003975:Diazepam / Q000494:pharmacology*; D004597:Electroshock / Q000009:adverse effects; D008297:Male; D019579:Neocortex / Q000293:injuries* / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D014465:Ultrasonics; D014828:Vocalization, Animal / Q000187:drug effects*
D014151:Anti-Anxiety Agents; D003975:Diazepam