Prelimbic α2-adrenoceptors are involved in the regulation of depressive-like behavior in hemiparkinsonian rats / 西安交通大学学报(医学版)

Objective: To observe the depressive-like behavior in hemiparkinsonian rats and the effects of activation or blockade of prelimbic (PrL) α2-adrenoceptors on depressive-like behavior in sham-operated and the parkinsonian rats. Methods: The rat model of Parkinson's disease (PD) was established by injection of 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle (MFB). Then the depressive-like behavior in rats was detected by the sucrose preference test and forced swim test (FST). In addition, changes in depressive-like behavior in the rats were also observed after local injection of a selective α2-adrenoceptor agonist or antagonist into the PrL. Results: The unilateral lesion of MFB by 6-OHDA induced depressive-like behavior as measured by the sucrose preference test and the FST compared to the sham-operated rats. Intra-PrL injection of selective α2-adrenoceptor agonist clonidine induced depressive-like behavior in the sham-operated and the lesioned rats. However, intra-PrL injection of α2-adrenoceptor antagonist idazoxan elicited anti-depressant effects in both the sham-operated and the lesioned groups. Moreover, the effective doses for behavior produced by clonidine and idazoxan in the lesioned rats were higher than those in the sham-operated rats. Conclusion: The α2-adrenoceptors in the PrL play an important role in the regulation of depressive-like behavior in PD.

Prelimbic α1-Adrenoceptors are involved in regulation of neural activities in the amygdala in a rat model of Parkinson's disease with anxiety / 西安交通大学学报(医学版)

Objective: To observe the effects of activation or blockade of the prelimbic (PrL) α1-adrenoceptors on anxiety-like behaviors and amygdaloid neural activities in rats with Parkinson's disease (PD). Methods: The rat model of PD was established by 6-hydroxydopamine (6-OHDA) unilateral lesion of the medial forebrain bundle (MFB). Then the anxiety-like behavior of rats was detected by the open field test. In addition, the changes of anxiety-like behavior, the effects of PrL α1-adrenoceptor stimulation on monoamines and c-Fos expression in the amygdala were also observed after local injection of the selective α1-adrenoceptor agonist or antagonist into the PrL by guided cannula. Results: Unilateral 6-OHDA lesions of the MFB in rats induced anxiety-like behaviors (P<0.001). Furthermore, activation of the PrL α1-adrenoceptors significantly induced or enhanced anxiety-like behaviors in the rats (sham group: P<0.001; lesion group: P<0.05), while blockade of the α1-adrenoceptors produced anxiolytic effects (sham group: P<0.001; lesion group: P<0.05). Then activation of the PrL α1-adrenoceptors increased the levels of DA and 5-HT while blockade of the PrL α1-adrenoceptors decreased DA and 5-HT levels in the amygdala in sham-operated rats (DA & 5-HT: P<0.001). However, compared to those of sham-operated rats, activation of the PrL α1-adrenoceptors increased the levels of NA and 5-HT while blockade of the PrL α1-adrenoceptors decreased NA and 5-HT levels in the amygdala in the lesioned rats (NA & 5-HT: P<0.001). In addition, the density of c-Fos immunoreactive positive neurons in the amygdala increased after intra-PrL injection α1-adrenoceptors agonist phenylephrine (sham group & lesion group: P<0.001). Conclusion: These findings indicate that changed neural activities in the amygdala after activation or blockade of the PrL α1-adrenoceptors are involved in regulating anxiety-like behaviors in PD rats.

Firing activity of locus coeruleus noradrenergic neurons increases in a rodent model of Parkinsonism / 神经科学通报·英文版

<p><b>OBJECTIVE</b>To investigate the changes in the firing activity of noradrenergic neurons in the locus coeruleus (LC) in a rat model of Parkinson disease (PD).</p><p><b>METHODS</b>2 and 4 weeks after unilateral lesion of the nigrostriatal pathway in the rat by local injection of 6-hydroxydopamine (6-OHDA) into the right substantia nigra pars compacta (SNc), the firing activity of noradrenergic neurons in LC was recorded by extracellular single unit recording.</p><p><b>RESULTS</b>The firing rate of LC noradrenergic neurons increased significantly 2 and 4 weeks after 6-OHDA lesions compared to normal rats, respectively (P < 0.05). The percentage of irregularly firing neurons was obviously higher than that of normal rats during the fourth week after SNc lesion (P < 0.05).</p><p><b>CONCLUSION</b>LC noradrenergic neurons are overactive and more irregular in 6-OHDA-lesioned rats. These changes suggest an implication of the LC in the pathophysiological mechanism of PD.</p>

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

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.