Responses of substantia nigra pars reticulata neurons to benzodiazepine ligands after acute and prolonged diazepam exposure. II. Modulation of firing rate.
We have examined the effects of chronic (3 week) and acute (1 hr) exposure to diazepam on firing rate responses of reticulata neurons to the inverse agonist methyl-6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM) and the benzodiazepine antagonist Ro15-1788. The ability of DMCM and Ro15-1788 to alter firing rate were tested in control, chronic diazepam and acute diazepam-treated rats. In controls, DMCM increased firing rate of reticulata neurons. This effect was reversed by Ro15-1788, which had no effect on firing rate when administered alone. In acute and chronic diazepam-treated groups, low doses of DMCM were less effective in increasing firing than in controls. However, the administration of high doses of DMCM to diazepam-treated animals increased firing rates above the rates observed in control animals after the same compounds. Administration of Ro15-1788 also increased reticulata firing rates above control levels in both acute and chronic diazepam-treated groups. The similarity in reticulata responses after chronic (3 week) and acute (1 hr) diazepam treatments suggests that the altered properties of the benzodiazepine ligands observed after chronic exposure could reflect the presence of diazepam. This may indicate that reticulata neurons themselves do not show changes in sensitivity to benzodiazepine ligands after chronic benzodiazepine exposure. We propose that the altered responses to DMCM and Ro15-1788 in diazepam-treated rats reflect a compensatory change which occurs by 1 hr and maintains reticulata activity at a constant level throughout the period of prolonged exposure to the agonist.
Wilson
M A
MA
Yale University School of Medicine, Department of Psychiatry, New Haven, Connecticut.
Gallager
D W
DW
D000818:Animals; D002243:Carbolines / Q000494:pharmacology; D003975:Diazepam / Q000494:pharmacology*; D005442:Flumazenil / Q000494:pharmacology; D008024:Ligands; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects*; D013378:Substantia Nigra / Q000187:drug effects* / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D002243:Carbolines; D008024:Ligands; D011963:Receptors, GABA-A; C034818:methyl 6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate; D005442:Flumazenil; D005680:gamma-Aminobutyric Acid; D003975:Diazepam