The dopaminergic agonist quinpirole triggers 5-HT2C receptor-dependent controls on both purposeless oral movements and the activity of the hyperdirect pathway in basal ganglia.
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1
Université Bordeaux Segalen, France
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2
Institut des Maladies Neurodegeneratives UMR CNRS 5293, France
Excessive dopamine (DA) transmission in associative/limbic areas of basal ganglia is thought to underline a variety of behavioral disorders including dyskinesia. The excessive DA tone promotes alterations on other neurochemical pathways and numerous authors have suggested that serotonergic (5-HT) controls, notably via the 5-HT2C receptor, are triggered in case of DA changes. The possible locations of the interaction between DA transmission and 5-HT2C receptors within basal ganglia are not known.
Here, we studied in Sprague-dawley male rats the contribution of 5-HT2C receptors using the 5-HT2C antagonist SB243213 in the effects elicited by the dopaminergic agonist quinpirole on both purposeless oral movements, c-Fos expression in basal ganglia nuclei and the electrophysiological activity of substantia nigra pars reticulata (SNr) neurons, the main output of basal ganglia, responding to the electrical stimulation of the cingular cortex.
The results showed that SB243213 (1mg/kg i.p.), without effect by itself, blocked the purposeless oral movements induced by 0.5 mg/kg i.p quinpirole. The levels of the protein c-Fos, barely affected by quinpirole or SB-243213, were significantly increased in the subthalamic nucleus (STN) when the treatments were combined. Similarly, in urethane-anesthetized rats, SB-243213 unmasked a facilitatory effect of quinpirole on the spontaneous discharge of SNr neurons (+40% compared to quinpirole alone). Interestingly, the effect elicited by the electrical stimulation of the cingular cortex (500-700 µA; 0.3 Hz), characterized by an excitatory-inhibitory-excitatory response in a small population of SNr neurons, was subtly changed by the drugs. Quinpirole did enhance the amplitude of the early excitatory response (+80% compared to saline-treated rats), involving the hyperdirect pathway and the STN, and this effect was abolished by the 5-HT2C receptor antagonist.
In conclusion, these results extend previous evidence that excessive DA tone triggers 5-HT2C receptors-dependent controls in basal ganglia. The interaction occurs likely on the hyperdirect pathway in line with the role of the STN in mediating the purposeless oral movements induced by DA and 5-HT2C agonists. 5-HT2C antagonism could be therapeutically relevant in limiting abnormal motor behaviors triggered by DA agonists.
Keywords:
PURPOSELESS ORAL MOVEMENT,
5-HT2c receptor,
Dopamine,
Basal Ganglia,
hyperdirect pathway,
Subthalamic Nucleus
Conference:
4th Conference of the Mediterrarnean Neuroscience Society, Istanbul, Türkiye, 30 Sep - 3 Oct, 2012.
Presentation Type:
Poster Presentation
Topic:
Abstracts
Citation:
LAGIERE
M,
BOSC
M and
De Deurwaerdère
P
(2013). The dopaminergic agonist quinpirole triggers 5-HT2C receptor-dependent controls on both purposeless oral movements and the activity of the hyperdirect pathway in basal ganglia..
Conference Abstract:
4th Conference of the Mediterrarnean Neuroscience Society.
doi: 10.3389/conf.fnhum.2013.210.00043
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Received:
25 Jan 2013;
Published Online:
11 Apr 2013.
*
Correspondence:
Miss. Mélanie LAGIERE, Université Bordeaux Segalen, BORDEAUX, France, melanie.lagiere@u-bordeaux2.fr