Tj. Sajdyk et A. Shekhar, Sodium lactate elicits anxiety in rats after repeated GABA receptor blockade in the basolateral amygdala, EUR J PHARM, 394(2-3), 2000, pp. 265-273
Repeated administration of the GABA(A) receptor antagonist bicuculline meth
iodide into the basolateral nucleus of the amygdala at doses subthreshold t
o eliciting a full response will eventually produce long-term 'priming', su
ch 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 l
ong-term priming of anxiety within the basolateral nucleus is producing a c
ondition similar to that seen in human panic disorder by testing the respon
se elicited by i.v, lactate infusions, since lactate infusions induce a pan
ic attack in patients with panic disorder. Male Wistar rats were fitted wit
h 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 el
icited a primed response, while the same procedure with artificial cerebros
pinal 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% salin
e in a random order separated by 48 h. Heart rate and blood pressure were m
onitored 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 i
ncreases in heart rate, blood pressure and experimental anxiety. Thus, rats
which are primed with chronic subthreshold GABA receptor blockade in the b
asolateral nucleus develop a sensitivity to sodium lactate, similar to huma
n panic disorder patients. (C) 2000 Elsevier Science B.V. All rights reserv
ed.