Precipitated withdrawal in the substantia nigra in diazepam-dependent female rats

Female rats were exposed to diazepam (DZ) implants (90 mg/week) or to empty capsules (controls) for 5 weeks. Rats were focally injected (1 microl) into the substantia nigra (SNR) with the central (CBR) and peripheral (PBR) benzodiazepine receptor antagonists, flumazenil [(FLU) 6.25, 12.5, or 25 microg], and PK 11195 [(PK) 3.125, 6.25, 12.5, or 25 microg], respectively. Rats were observed for behavioral and EEG manifestation of withdrawal syndrome. In female rats, both FLU and PK induced a dose-related precipitated abstinence score (PAS), tachypnea, and head bobbing. Twitches and jerks tended to increase with increasing dose of both FLU and PK. Furthermore, FLU evoked dose-related turning and head and body tremors. The FLU- and the PK-induced PAS were accompanied by an increase in total power of the EEG in the SNR. The involvement of the CBR and PBR in physical dependence on DZ in the SNR is suggested. The present data in female rats are discussed with regard to similarities and differences with previous studies in male rats.