Substantia Nigra: The Involvement of Central and Peripheral Benzodiazepine Receptors in Physical Dependence on Diazepam as Evidenced by Behavioral and EEG Effects

摘要: Abstract Male rats chronically exposed to diazepam (DZ) slowly released from subcutaneously implanted silastic capsules along with empty capsule control were focally injected (1 μl) into the substantia nigra (SNR) central (CBR) and peripheral (PBR) benzodiazepine receptor antagonists, flumazenil [(FLU) 6.25, 12.5, 25 μg] PK 11195 [(PK) 3.125, μg], respectively (weekly intervals; Latin square design). Rats observed for signs of withdrawal EEG was recorded simultaneously site injection (SNR), caudate putamen, thalamus, hippocampus, frontal cortex. In DZ-dependent Precipitated Abstinence Score (PAS) significantly related dose FLU. The PAS increased increasing doses (3.125–12.5 μg); however, highest (25 μg) showed less effect. rapid onset accompanied by a rise in total power (1–32 Hz) (TPEEG) SNR other brain areas. TPEEG had similar time courses. Intranigrally FLU did not evoke clonic tonic–clonic convulsions; both antagonists induced dose-related twitches jerks. Additionally, precipitated tachypnea increases turning backing. Chronic DZ treatment altered spectral content EEG, as indicated decrease an increase slow fast frequency bands, respectively. rapidly but transiently reversed EEG. Data suggest that CBR mediate autonomic motor withdrawal, while PBR are responsible jerks alteration It is possible also acts on linked GABAA/CBR/ionophore.