A single injection of cocaine (24 hr prior to injection of carbamazepine) caused a trend (p=0.06) toward increased plasma levels of carbamazepine (single injection). More studies are required to test the effects of chronic cocaine treatment on carbamazepine plasma levels. These data suggest that carbamazepine treatment of humans for cocaine withdrawal may require close monitoring of carbamazepine blood levels to prevent potential toxic effects of this drug. Studies were started to investigate the gamma-aminobutyric acid (GABA-A) receptor system in amygdala-kindled rats that were made contingent tolerant to the anticonvulsant effects of diazepam. A study parallel to this one using contingent tolerance to carbamazepine was reported in last year's project report (Z01 MH 02459-06 BPB). Thus far, only the alpha-4 subunit of the GABA-A receptor has been measured. Results were qualitatively the same as for tolerance to carbamazepine. Kindling increased mRNA for the alpha-4 subunit selectively in the dentate gyrus of the hippocampus, and this increase was significantly less in rats tolerant to diazepam. However, the increase in rats tolerant to diazepam was greater than that observed in carbamazepine-tolerant rats.
