Septal driving of hippocampal theta rhythm: role of gamma-aminobutyrate-benzodiazepine receptor complex in mediating effects of anxiolytics.
In free-moving male rats, when the hippocampal theta rhythm is artificially driven by stimulation in the septum at frequencies between 5 and 10 Hz, the function relating frequency to the threshold current required to drive the theta rhythm has a minimum at 7.7 Hz. This minimum is eliminated by anxiolytic drugs. Dose-response curves for this effect are reported for chlordiazepoxide, diazepam and meprobamate. The effect of meprobamate was reversed by two gamma-aminobutyrateA antagonists, picrotoxin and bicuculline, which have previously been shown to be without effects of their own. The gamma-aminobutyrateB agonist, baclofen, also without effect on its own, blocked the elimination of the 7.7-Hz minimum caused by the gamma-aminobutyrateA agonist, muscimol. The beta-carboline, ethyl-beta-carboline-3-carboxylate, had mixed agonist/antagonist properties, blocking the effects of chlordiazepoxide, diazepam and muscimol (though not sodium amylobarbitone) but itself acting like a benzodiazepine. Coupled with earlier data, these findings support a role for gamma-aminobutyrate receptors in mediating the effects of anxiolytic drugs.
Quintero
S
S
Mellanby
J
J
Thompson
M R
MR
Nordeen
H
H
Nutt
D
D
McNaughton
N
N
Gray
J A
JA
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001418:Baclofen / Q000494:pharmacology; D002243:Carbolines / Q000494:pharmacology; D002707:Chlordiazepoxide / Q000494:pharmacology; D003975:Diazepam / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects*; D008297:Male; D008620:Meprobamate / Q000494:pharmacology; D009434:Neural Pathways / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects*; D012688:Septum Pellucidum / Q000187:drug effects*; D013826:Theta Rhythm
D014151:Anti-Anxiety Agents; D002243:Carbolines; D011963:Receptors, GABA-A; D002707:Chlordiazepoxide; C024915:beta-carboline-3-carboxylic acid ethyl ester; D008620:Meprobamate; D001418:Baclofen; D003975:Diazepam