GABA modulation of the defense reaction induced by brain electrical stimulation

Earlier behavioral results led to the suggestion that GABA exerts a tonic inhibitory influence in the dorsal periaqueductal gray (DPAG) matter of the rat integrating defensive behavior. In the present experiments, the role of GABAergic mechanisms in the modulation of the autonomic component of the defense reaction was studied. Thus, the effects of intravenous (IV) injections of chlordiazepoxide as well as of intracerebral (IC) injections of midazolam in the dorsal midbrain, on the blood pressure (BP), heart rate (HR) and respiratory increases induced by electrical stimulation of the DPAG were measured in rats anesthetized with urethane. Chlordiazepoxide (10 mg/kg, IV) as well as midazolam (40 and 160 nmol, IC) attenuated the centrally-induced hypertension, without affecting basal BP. The tachycardia induced by aversive brain stimulation was similarly decreased by the benzodiazepines. In addition, the HR baseline was significantly raised by chlordiazepoxide and by the highest dose of midazolam. The tachypnea induced by brain electrical stimulation was also reduced by both benzodiazepines. Basal respiratory rate was slightly, but significantly decreased by chlordiazepoxide as well as by the two doses of midazolam used and to a lesser extent by the vehicle alone. Chlordiazepoxide attenuated the increase in respiratory depth caused by brain stimulation, while basal respiratory amplitude was not affected. The effects of midazolam on this parameter were unclear. Microinjection of bicuculline (5 and 10 nmol) or picrotoxin (0.3 and 1 nmol) into the DPAG increased the BP, HR and respiration, like the electrical stimulation. The latency and duration of bucuculline effects were shorter than those of picrotoxin.(ABSTRACT TRUNCATED AT 250 WORDS)