Lidocaine, carbamazepine, and valproic acid were found to have greater potency for displacing [3H]Ro5-4864 than [3H]PK-11195 at the PBR in olfactory bulb. These results suggest that the anticonvulsant or convulsant effects of these drugs may involve a PBR component. [3H]PK-11195 binding in the olfactory bulb revealed increased density and decreased affinity of PBR in amygdala-kindled rats receiving multiple stage 5 seizures compared with sham control rats 24 hr after the last seizure. We plan to test PBR binding in other brain regions (e.g., hippocampus, cerebral cortex, striatum, cerebellum) to determine whether kindling alters this system in selective brain regions. It was recently reported by others that the PBR are involved in stereogenesis by increasing cholesterol transport into mitochondria. Preliminary data in our laboratory suggest that carbamazepine also increases cholesterol uptake by rat brain mitochondria with resultant increased cholesterol metabolism (presumably steroid production). Since carbamazepine binds with PBR, we hypothesize that (and plan to determine whether) carbamazepine does increase steroid synthesis in rat brain. This may be an important effect of the CNS effects of carbamazepine. It was found that sulfonated dyes, Fast Green FCF and Brilliant Blue FCF, stimulated Poly (ADP-ribosylation) in rat brain nuclei by a mechanism that appears to be devoid of DNA damage. The structurally related dye Light Green SF Yellowish was inhibitory by itself and dose-dependently inhibited the stimulatory effects of Fast Green FCF. The sulfonated dyes may become important tolls for elucidating the mechanism of action of the chromatin bound enzyme poly(ADP-ribose) polymerase.
