Sodium lactate elicits anxiety in rats after repeated GABA receptor blockade in the basolateral amygdala

Repeated administration of the GABA(A) receptor antagonist bicuculline methiodide into the basolateral nucleus of the amygdala at doses subthreshold to eliciting a full response will eventually produce long-term 'priming', such that heart rate, blood pressure as well as anxiety are increased at the lower doses. The present study was conducted in order to determine if the long-term priming of anxiety within the basolateral nucleus is producing a condition similar to that seen in human panic disorder by testing the response elicited by i.v. lactate infusions, since lactate infusions induce a panic attack in patients with panic disorder. Male Wistar rats were fitted with femoral arterial and venous catheters and chronic microinjection cannulae into the basolateral nucleus. Repeated daily injections of a subthreshold dose of bicuculline methiodide into the basolateral nucleus for 4-5 days elicited a primed response, while the same procedure with artificial cerebrospinal fluid vehicle (a-CSF; sham-primed) had no effect. Following priming, rats received both sodium lactate infusions (0.5 N, 10 ml/kg) or 0.9% saline in a random order separated by 48 h. Heart rate and blood pressure were monitored throughout the infusion and the animals were immediately placed in the social interaction test to assess their anxiety response. Only primed and not sham-primed rats responded to a lactate infusion with significant increases in heart rate, blood pressure and experimental anxiety. Thus, rats which are primed with chronic subthreshold GABA receptor blockade in the basolateral nucleus develop a sensitivity to sodium lactate, similar to human panic disorder patients.