Septal driving of hippocampal theta rhythm: A role for γ-aminobutyrate in the effects of minor tranquillizers?

In 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 at that frequency has a minimum at 7.7 Hz. The minor tranquillizers chlordiazepoxide and amobarbital sodium abolish this minimum and it has been proposed that this action correlates with their anxiolytic effects. The flattening of the curve produced by chlordiazepoxide (5 mg/kg) was antagonized by picrotoxin (0.75 mg/kg) but not by bicuculline (2.5 mg/kg). The flattening produced by amobarbital sodium (15 mg/kg) was not antagonized by either picrotoxin (2 mg/kg) or bicuculline (2.5 mg/kg).Muscimol, a γ-aminobutyrate agonist, acted like a minor tranquillizer on the theta-driving curve. The dose response-curve for this effect was an inverted-U and the muscimol still produced significant flattening at a dose of less than 0.001 mg/kg. The effect of muscimol was antagonized by bicuculline (2.5 mg/kg) but not by picrotoxin (2 mg/kg).The results are discussed in relation to the hypothesis that γ-aminobutyrate may be involved in anxiety.