title: Lead intoxication induces noradrenaline depletion, motor nonmotor disabilities, and changes in the firing pattern of subthalamic nucleus neurons.
abstract: Lead intoxication has been suggested as a high risk factor for the development of Parkinson disease. However, its impact on motor and nonmotor functions and the mechanism by which it can be involved in the disease are still unclear. In the present study, we studied the effects of lead intoxication on the following: (1) locomotor activity using an open field actimeter and motor coordination using the rotarod test, (2) anxiety behavior using the elevated plus maze, (3) "depression-like" behavior using sucrose preference test, and (4) subthalamic nucleus (STN) neuronal activity using extracellular single unit recordings. Male Sprague-Dawley rats were treated once a day with lead acetate or sodium acetate (20 mg/kg/d i.p.) during 3 weeks. The tissue content of monoamines was used to determine alteration of these systems at the end of experiments. Results show that lead significantly reduced exploratory activity, locomotor activity and the time spent on the rotarod bar. Furthermore, lead induced anxiety but not "depressive-like" behavior. The electrophysiological results show that lead altered the discharge pattern of STN neurons with an increase in the number of bursting and irregular cells without affecting the firing rate. Moreover, lead intoxication resulted in a decrease of tissue noradrenaline content without any change in the levels of dopamine and serotonin. Together, these results show for the first time that lead intoxication resulted in motor and nonmotor behavioral changes paralleled by noradrenaline depletion and changes in the firing activity of STN neurons, providing evidence consistent with the induction of atypical parkinsonian-like deficits.
authors.affiliation: Univ. de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, F-33000 Bordeaux, France.
authors.forename: M
authors.initials: M
authors.lastname: Sabbar
authors.forename: C
authors.initials: C
authors.lastname: Delaville
authors.forename: P
authors.initials: P
authors.lastname: De Deurwaerdère
authors.forename: A
authors.initials: A
authors.lastname: Benazzouz
authors.forename: N
authors.initials: N
authors.lastname: Lakhdar-Ghazal
mesh_terms: D000818:Animals; D001007:Anxiety / Q000139:chemically induced; D003863:Depression / Q000139:chemically induced; D020263:Lead Poisoning, Nervous System / Q000378:metabolism / Q000503:physiopathology*; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism*; D020734:Parkinsonian Disorders / Q000378:metabolism / Q000503:physiopathology; D018408:Patch-Clamp Techniques; D017207:Rats, Sprague-Dawley; D020531:Subthalamic Nucleus / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology
chemical_list: D009638:Norepinephrine