Responses of substantia nigra pars reticulata neurons to benzodiazepine ligands after acute and prolonged diazepam exposure. I. Modulation of gamma-aminobutyric acid sensitivity.
We have examined the ability of the benzodiazepine inverse agonist, methyl-6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM), and the antagonist, Ro15-1788, to modulate gamma-amino-butyric acid (GABA) sensitivity of reticulata neurons after chronic (3 week) and acute (1 hr) diazepam exposure. Sensitivity to GABA was analyzed by monitoring single unit responses to microiontophoretically applied GABA. The inverse agonist DMCM decreased GABA sensitivity of reticulata neurons to similar levels in control, chronic diazepam and acute diazepam-treated groups. Ro15-1788 administration reversed the effects of DMCM on GABA sensitivity and also resulted in comparable levels of GABA sensitivity in all treatment groups. Thus, the ability of the inverse agonist DMCM and the antagonist Ro15-1788 to alter GABA sensitivity of reticulata neurons was not altered by diazepam treatment. However, reticulata GABA sensitivity in the absence of additional benzodiazepine ligands was enhanced in both acute and chronic diazepam groups when compared to control values. The similarity in reticulata responses after both chronic (3 week) and acute (1 hr) diazepam treatments suggests that the enhanced sensitivity to GABA merely reflects the presence of diazepam. Thus, the ability of diazepam to potentiate reticulata GABA responses does not show time-dependent changes with prolonged benzodiazepine exposure.
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; D005479:Flurazepam / Q000494:pharmacology; D008024:Ligands; D008297:Male; D009474:Neurons / Q000187:drug effects; 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; D005479:Flurazepam; D003975:Diazepam