Involvement of basal ganglia network in motor disabilities induced by typical antipsychotics
PLoS ONE. 2009-07-09; 4(7): e6208
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1. PLoS One. 2009 Jul 9;4(7):e6208. doi: 10.1371/journal.pone.0006208.
Involvement of Basal Ganglia network in motor disabilities induced by typical
Chetrit J(1), Ballion B, Laquitaine S, Belujon P, Morin S, Taupignon A, Bioulac
B, Gross CE, Benazzouz A.
(1)Université de Bordeaux, Bordeaux, France.
BACKGROUND: Clinical treatments with typical antipsychotic drugs (APDs) are
accompanied by extrapyramidal motor side-effects (EPS) such as hypokinesia and
catalepsy. As little is known about electrophysiological substrates of such motor
disturbances, we investigated the effects of a typical APD, alpha-flupentixol, on
the motor behavior and the neuronal activity of the whole basal ganglia nuclei in
METHODS AND FINDINGS: The motor behavior was examined by the open field actimeter
and the neuronal activity of basal ganglia nuclei was investigated using
extracellular single unit recordings on urethane anesthetized rats. We show that
alpha-flupentixol induced EPS paralleled by a decrease in the firing rate and a
disorganization of the firing pattern in both substantia nigra pars reticulata
(SNr) and subthalamic nucleus (STN). Furthermore, alpha-flupentixol induced an
increase in the firing rate of globus pallidus (GP) neurons. In the striatum, we
recorded two populations of medium spiny neurons (MSNs) after their antidromic
identification. At basal level, both striato-pallidal and striato-nigral MSNs
were found to be unaffected by alpha-flupentixol. However, during electrical
cortico-striatal activation only striato-pallidal, but not striato-nigral, MSNs
were found to be inhibited by alpha-flupentixol. Together, our results suggest
that the changes in STN and SNr neuronal activity are a consequence of increased
neuronal activity of globus pallidus (GP). Indeed, after selective GP lesion,
alpha-flupentixol failed to induce EPS and to alter STN neuronal activity.
CONCLUSION: Our study reports strong evidence to show that hypokinesia and
catalepsy induced by alpha-flupentixol are triggered by dramatic changes
occurring in basal ganglia network. We provide new insight into the key role of
GP in the pathophysiology of APD-induced EPS suggesting that the GP can be
considered as a potential target for the treatment of EPS.
PMID: 19587792 [Indexed for MEDLINE]