Bicuculline administration into ventromedial hypothalamus: effects on fear and regional brain monoamines and GABA concentrations in rats.

The effects of bicuculline methiodide administration into ventromedial hypothalamus (15 ng per site, bilaterally) on fear behavior and monoamines (NA, DA, 5-HT) and GABA in structures of the brain defensive system (hypothalamus, midbrain gray matter, amygdala, hippocampus and frontal cortex) were studied. Fear behavior was examined in the modified version of light-dark transition test. The time out from the illuminated compartment of chamber, the time spent there and number of returns to the illuminated compartment was measured. Additionally motor activity, i.e., number of crossings and rearings in dark as well as in the illuminated part of compartment, was registered. Blockade of GABAA receptors in the ventromedial hypothalamus resulted in increased fear behavior, i.e. decrease of time out from illuminated compartment and decrease of the time spent there. Motor behavior remained unchanged. HPLC analysis showed reduction of GABA concentration in all investigated brain structures. An increase of NA concentration in all examined structures with exception of the hypothalamus without effect on MHPG/NA was observed as well. Dopamine level remained unchanged, but DOPAC/DA ratio increased in all structures, except frontal cortex. Also HVA/DA ratio increased in the hypothalamus and midbrain. 5-HT concentration increased only in midbrain, 5-HIAA increased in midbrain and in frontal cortex, and 5-HIAA/5-HT ratio increased only in frontal cortex. These results indicate that GABA-ergic and monoaminergic systems remain in functional interactions and that these interactions may play an important role in the neurochemical regulation of fear behavior. The possible mechanism of GABA--monoaminergic interactions is discussed.