Serotonin and norepinephrine depletions can promote anxiety and depression in a rat model of Parkinson’s disease: an electrophysiological and behavioural study.
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1
National Institutes of Health, NINDS, United States
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2
CNRS, Neurodegenerative Diseases Institute UMR 5293, France
The loss of dopamine (DA) neurons has been the pathophysiological focus of the devastating motor conditions of Parkinson’s disease (PD). Beyond DA, PD is a multi-system disorder characterized also by the loss of serotonin (5-HT) neurons from the dorsal raphe nucleus and norepinephrine (NE) neurons from the locus coeruleus. 5-HT and NE are widely recognized in the development of depression and anxiety and both symptoms are reported with a high prevalence in PD patients. However, a specific role for each neurotransmitter in the pathophysiology of PD is not clearly determined.
Here, we investigated, in rats, the respective influence of DA, 5-HT and NE depletions on motor and non-motor behaviors as well as on the neuronal activity measured in vivo by single cell extracellular recordings in subthalamic (STN), globus pallidus (GP) and substantia nigra pars reticulata (SNr). DA, 5-HT and NE depletions were achieved by using classic protocols with 6-hydroxydopamine/desipramine, parachlorophenylalanine and DSP-4, respectively.
We showed that NE or DA, but not 5-HT depletion significantly decreased locomotor activity and enhanced the proportion of bursty and irregular STN neurons. Anxiety-like states required DA depletion plus the depletion of 5-HT or NE. Anhedonia and “depressive-like” behavior emerged only from the combined depletion of all three monoamines, an effect paralleled by an increase in the firing rate and the proportion of bursty and irregular STN neurons. As for the STN, DA depletion increased the proportion of bursty neurons in GP and SNr. 5-HT, but not NE depletion modified GP and SNr neuronal activity.
Thus, our data show that 5-HT and NE modulate specifically the basal ganglia activity and provides evidence for the exacerbation of behavioral deficits when 5-HT and/or NE depletions are combined with DA depletion. These data bring up new insight into the influence of 5-HT system in non-motor symptoms of PD.
Keywords:
Parkinson Disease,
Norepinephrine,
Serotonin,
non-motor symptoms,
Motor Activity
Conference:
4th Conference of the Mediterrarnean Neuroscience Society, Istanbul, Türkiye, 30 Sep - 3 Oct, 2012.
Presentation Type:
Symposium
Topic:
Abstracts
Citation:
Delaville
C,
Chetrit
J,
Navailles
S,
De Deurwaerdère
P and
Benazzouz
A
(2013). Serotonin and norepinephrine depletions can promote anxiety and depression in a rat model of Parkinson’s disease: an electrophysiological and behavioural study..
Conference Abstract:
4th Conference of the Mediterrarnean Neuroscience Society.
doi: 10.3389/conf.fnhum.2013.210.00022
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Received:
26 Jan 2013;
Published Online:
11 Apr 2013.
*
Correspondence:
Dr. Claire Delaville, National Institutes of Health, NINDS, Bethesda, Maryland, MD 20892-3702, United States, cdelaville@gmail.com