Effects of GABAB, 5-HT1A, and 5-HT2 receptor stimulation on activation and inhibition of the rat lateral amygdala following medial geniculate nucleus stimulation in vivo

The input from the medial geniculate nucleus of the thalamus (MGN) to the lateral amygdala is known to be important in the regulation of fear and anxiety. Modulation of this pathway may be useful for the treatment of anxiety disorders. We set out to determine whether simple extracellular electrophysiological techniques could be used to study pharmacological modulation of this pathway in vivo. We studied the effects of GABAB, 5-HT1, and 5-HT2 receptor agonists on activity in the lateral amygdala following stimulation of the MGN in isoflurane-anaesthetised rats. Electrical stimulation of the MGN evoked a characteristic biphasic field potential in the lateral amygdala. Baclofen (10 mg kg−1, iv) inhibited the evoked potential with an effect that was most marked on the positive-going component (80±9% inhibition; P<0.05). Baclofen also significantly reduced paired-pulse inhibition of the negative-going component at short interpulse intervals (<200 ms). The 5-HT1A receptor ligands, 8-OH-DPAT (60 μg kg−1, iv) and WAY-100635 (0.5 mg kg−1, iv) were without effect on evoked responses or paired-pulse relationship. In contrast, the 5-HT2 receptor agonist, DOI, caused a rapid inhibition of the field potential (to 59.33±11.41% of the baseline response; P<0.05). This effect was blocked by ketanserin, either following systemic (0.5 mg kg−1, iv) or intra-amygdala administration. These results show that GABAB and 5-HT2 receptor agonists can modulate activation of the lateral amygdala following MGN stimulation; furthermore, GABAB receptor agonists appear to have a profound effect on local circuit inhibition within the lateral amygdala. The results support the use of in vivo field potential recording within the MGN-lateral amygdala pathway to evaluate this as a possible site of action for novel anxiolytic drugs.