PRIMING OF EXPERIMENTAL ANXIETY BY REPEATED SUBTHRESHOLD GABA BLOCKADE IN THE RAT AMYGDALA

Blockade of GABA(A) receptor function in the area of the anterior basolateral amygdala of rats elicits physiological (increases in heart rate and blood pressure) and behavioral changes similar to symptoms of human anxiety states. Repeated subthreshold blockade of GABA(A) receptors in this region appears to result in a long-term 'priming' of these anxiety-like responses. The present study was conducted to characterize the 'priming' of the heart rate and blood pressure responses and to test if these 'primed' animals would show increases in anxiety responses. Male Wistar rats with arterial catheters placed for physiological measurements were implanted with chronic microinjection cannulae in the anterior basolateral amygdaloid nucleus (BLA) under pentobarbital anesthesia. Repeated daily injections of a subthreshold dose of bicuculline methiodide (GABA(A) receptor antagonist; BMI) into the BLA elicited 'priming' of physiological responses after 3-5 injections and this response was maintained for at least 6 weeks. The primed animals also showed increased anxiogenic responses to GABA(A) blockade in the BLA. The 'priming' of anxiety responses were clearly elicited before kindling of seizures as measured by EEG. These results suggest that this 'priming' phenomenon may be similar to kindling and long-term potentiation. This could be one potential mechanism for developing pathological emotional responses, such as chronic, high levels of anxiety.