Effects of GABAA and GABAB receptor agonists on reticular-elicited hippocampal rhythmical slow activity

Hippocampal rhythmical slow activity (RSA) can be elicited by stimulation of the midbrain reticular formation. All classes of anxiolytic drug so far tested reduce the frequency of this RSA. Anxiolytic barbiturates and benzodiazepines, as opposed to compounds such as buspirone, are thought to act as receptor agonists of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). In the present study muscimol (a GABAA receptor agonist) and baclofen (a GABAB receptor agonist) were injected into freely moving rats. Baclofen produced a dose-related decrease in frequency of RSA in the range 1 to 9 mg/kg i.p. and abolished RSA at 27 mg/kg. Muscimol produced an increase in RSA frequency with an inverted U-shaped dose response curve in the range 0.0001 to 1.0 mg/kg with maximal effect at 0.001 mg/kg. The effects of classical anxiolytic drugs in the present test resemble those of the GABAB receptor agonist baclofen more than they resemble those of the GABAA receptor agonist muscimol but it is possible that they are acting via GABA systems which employ low rather than high affinity GABAA receptors or through some transmitter system other than GABA.