Picrotoxin, a gamma-aminobutyric acid-receptor antagonist, retards craniofacial development in the weaning rat: I. Effect on mandibular bone growth.

The in vivo effects of elevated doses of picrotoxin, a gamma-aminobutyric acid (GABA) A-receptor antagonist, were studied in the skulls of weaning rats. Twenty-one-day-old male rats were treated daily with 2 mg/kg of pictroxin for a period of 3 weeks. This study revealed that chronic administration of the agent caused a reduction in bone formation in various growth sites in the skull along with a significant decrease in the calcium content and alkaline phosphatase activity in the mandible. Serum levels of calcium were unchanged, but the activity of alkaline phosphatase decreased. The decrease in bone alkaline phosphatase was accompanied by structural changes in the developing mandible. The latter was manifested by qualitative changes in the structure of ossification sites, in the appearance of the osteoblasts, and in the pattern of bone mineralization. These findings indicate that picrotoxin affects the normal growth of the craniofacial skeleton in an intact growing animal, probably because of central changes in GABA-ergic control on motor function along with possible alteration in corticosteroid secretion.