Picrotoxin, a gamma-aminobutyric acid-receptor antagonist, retards craniofacial development in the weaning rat: II. Effect on mandibular condylar cartilage.

The in vivo effects of picrotoxin, a gamma-aminobutyric acid (GABA)-receptor antagonist, were studied in the mandibular condyles of weaning rats. Male rats 21 days old were treated daily with 2 mg/kg of picrotoxin for a period of 3 weeks. This study revealed that chronic administration of the agent caused a reduction in bone formation in various sites in the mandible, along with significant changes in the structure of the condylar cartilage and its ossification front. The length of the chondroblastic zone increased, yet the length of the hypertrophic zone was reduced. The latter phenomenon was manifested by qualitative changes in the overall structure of various cellular zones, in the appearance of the osteoblasts, and in the pattern of cartilage mineralization. The changes in the condylar cartilage cannot be attributed to a direct effect of picrotoxin; in vitro studies indicated no significant change in the incorporation of 3H-thymidine and 35S-sulfate in picrotoxin-treated cultures. These findings indicate that picrotoxin affects the normal growth of the mandible in an intact, growing animal, probably through an indirect route involving neurons in the central nervous system.