The Levels of Somatostatin in the Brain and CSF of Rat after Carbamazepine Administration

Abstract

Previous studies have suggested that carbamazepine (CBZ), a potent antiepileptic drug, affects the somatostatinergic system in humans and animals; but the results have been contradictory. In the present study we further evaluated the effect of CBZ administration on somatostatin-like immunoreactivity (SLI) in cisternal cerebrospinal fluid (CSF) and in different areas of the rat brain. Somatostatin receptor binding in the cortex of CBZ-treated rats was also studied. Two hours after administration of CBZ at a dose of 30 mg/kg intraperitoneally, which resulted in a serum CBZ concentration of 64 microM, the SLI in CSF was lower than in vehichle-injected controls (P = 0.024, MANOVA). In the hippocampus SLI was elevated to 132% that of vehicle-injected controls (P = 0.016, Mann-Whitney U-test). At a dose of 15 mg/kg a slight decrease in SLI was seen in CSF compared to vehicle-injected controls (P = 0.034, MANOVA) but no change was observed in the hippocampus. After administration of CBZ for 7 days (30 mg/kg intraperitoneally twice a day) we were not able to demonstrate any definitive change in SLI of rat CSF (MANOVA). In these rats the SLI in the hypothalamus was elevated compared to vehicle-injected controls (132%, P = 0.016, Mann-Whitney U-test). In experiments with both acute and chronic administration of CBZ, the somatostatin receptor binding was unchanged. The present study suggests that administration of CBZ only slightly affects the somatostatinergic system in the rat brain.