Dorsal raphe and substantia nigra response to flumazenil in diazepam-dependent rats

Flumazenil (FLU; 25 micrograms) and DMSO-vehicle were focally injected (1 microliter) into the substantia nigra (SN) and the dorsal raphe nucleus (DR) in rats chronically implanted with silastic capsules containing diazepam (DZ; 540 mg/week). FLU precipitated an abstinence syndrome in the SN as indicated by a significant abstinence score, several abstinence signs and reduced total power of the fast frequency bands of the electroencephalogram (EEG) in the injections sites frontal cortex, (FC) and hippocampus (H). In contrast, FLU did not produce an abstinence syndrome in the DR, and its effect on the power of the EEG in DR, FC and H was not significantly different from that of the DMSO-vehicle. The data show regional heterogeneity in the response of the SN and the DR to chronic DZ treatment in terms of a focally precipitated abstinence syndrome.