title: Involvement of Basal Ganglia network in motor disabilities induced by typical antipsychotics.
abstract: 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 the rat.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Université de Bordeaux, Bordeaux, France.
authors: Jonathan
authors: J
authors: Chetrit
authors: Bérangère
authors: B
authors: Ballion
authors: Steeve
authors: S
authors: Laquitaine
authors: Pauline
authors: P
authors: Belujon
authors: Stéphanie
authors: S
authors: Morin
authors: Anne
authors: A
authors: Taupignon
authors: Bernard
authors: B
authors: Bioulac
authors: Christian E
authors: CE
authors: Gross
authors: Abdelhamid
authors: A
authors: Benazzouz
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000009:adverse effects*; D001479:Basal Ganglia / Q000503:physiopathology*; D001480:Basal Ganglia Diseases / Q000139:chemically induced / Q000503:physiopathology*; D003342:Corpus Striatum / Q000187:drug effects; D005475:Flupenthixol / Q000009:adverse effects*; D008297:Male; D051381:Rats; D017208:Rats, Wistar
chemical_list: D014150:Antipsychotic Agents; D005475:Flupenthixol