The selective 5-HT(1A) receptor antagonist WAY-100635 increases neuronal activity of the basolateral nucleus of the amygdala in 6-hydroxydopamine-lesioned rats

Abstract

In the present study, extracellular recording was used to examine the neuronal activity of the basolateral nucleus (BL) of the amygdala and the effects of systemic administration of the selective 5-HT(1A) receptor antagonist WAY-100635 on the neuronal activity in the normal rats and rats with 6-hydroxydopamine (6-OHDA)-produced lesions in the substantia nigra pars compacta (SNc). The results showed that the firing rates of BL projection neurons and interneurons were (0.39±0.04) Hz and (0.83±0.16) Hz in the normal rats, and (0.32±0.04) Hz and (0.53±0.12) Hz in 6-OHDA-lesioned rats. There was no significant difference in the firing rates of BL projection neurons and interneurons between the normal and 6-OHDA-lesioned rats. In the normal rats, all BL projection neurons fired in burst; 94% of BL interneurons fired in burst and 6% fired irregularly. In 6-OHDA-lesioned rats, 85% of BL projection neurons displayed a burst firing pattern and 15% fired irregularly; 86% of BL interneurons had a burst firing pattern and 14% fired irregularly. The distribution of firing patterns of projection neurons and interneurons in the BL in 6-OHDA-lesioned rats did not differ from that in the normal rats. Systemic administration of WAY-100635 at 0.1 mg/kg body weight did not change the mean firing rates of projection neurons and interneurons in the BL in both normal and 6-OHDA-lesioned rats. However, a higher dose of WAY-100635 at 0.5 mg/kg body weight significantly decreased the mean firing rate of BL projection neurons from (0.43±0.07) to (0.15±0.02) Hz in the normal rats (P<0.01), but significantly increased the activity of BL projection neurons in 6-OHDA-lesioned rats from (0.37±0.08) to (0.69±0.18) Hz (P<0.004). The mean firing rates of BL interneurons in the normal and 6-OHDA-lesioned rats did not change after administration of a higher dose of WAY-100635 at 0.5 mg/kg body weight. These results demonstrate that the activity of BL neurons after substantia nigra dopaminergic lesion in the SNc is regulated by activation of intrinsic and extrinsic inputs, and that 5-HT(1A) receptors significantly contribute to the regulation of the activity of BL projection neurons in both normal and 6-OHDA-lesioned rats. Furthermore, WAY-100635 induced an increase in the mean firing rate of projection neurons in the BL in 6-OHDA-lesioned rats, suggesting that 5-HT(1A) receptor is likely to play a role in generating affective symptoms in Parkinson's disease.