Effects of anxiolytic drugs on escape behavior induced by dorsal central gray stimulation in rats.
Each animal was chronically implanted with bipolar electrodes in dorsal central gray matter (DCG) and was trained to press a lever to decrease the DCG-stimulation current. Chlordiazepoxide (5-20 mg/kg, PO), diazepam (2-10 mg/kg, PO) and bromazepam (1-5 mg/kg, PO) produced dose-dependent increases in the DCG-stimulation threshold 1-4 h after administration without affecting motor performance. Meprobamate (200 mg/kg, PO) and pentobarbital (10 mg/kg, PO) also slightly increased the stimulation threshold. Their potency was in the order of bromazepam greater than diazepam greater than chlordiazepoxide greater than pentobarbital greater than meprobamate. The increase in the threshold induced by diazepam (10 mg/kg, PO) was inhibited by the GABA antagonists, bicuculline (1 mg/kg, IP) and picrotoxin (0.1 mg/kg, IP). These results suggest that decreased susceptibility to brain stimulation is involved in suppressing effects of anxiolytic drugs on the escape behavior, and also that the antiaversive action of benzodiazepines may be related to a GABAergic mechanism.
Gomita
Y
Y
Department of Hospital Pharmacy, Okayama University Medical School, Japan.
Moriyama
M
M
Ichimaru
Y
Y
Araki
Y
Y
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001143:Arousal / Q000187:drug effects*; D001362:Avoidance Learning / Q000187:drug effects*; D001640:Bicuculline / Q000494:pharmacology; D001931:Brain Mapping; D001960:Bromazepam / Q000494:pharmacology; D002707:Chlordiazepoxide / Q000494:pharmacology; D003975:Diazepam / Q000494:pharmacology*; D004558:Electric Stimulation; D004924:Escape Reaction / Q000187:drug effects*; D018756:GABA Antagonists; D008297:Male; D008620:Meprobamate / Q000494:pharmacology; D010424:Pentobarbital / Q000494:pharmacology; D010487:Periaqueductal Gray / Q000187:drug effects*; D010852:Picrotoxin / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012684:Sensory Thresholds / Q000187:drug effects
D014151:Anti-Anxiety Agents; D001640:Bicuculline; D001960:Bromazepam; D002707:Chlordiazepoxide; D003975:Diazepam; D018756:GABA Antagonists; D008620:Meprobamate; D010424:Pentobarbital; D010852:Picrotoxin