title: Postnatal inorganic lead exposure decreases the number of spontaneously active midbrain dopamine neurons in the rat.
abstract: This study examined the effect of lead (Pb) exposure during postnatal development on the electrophysiological activity of midbrain dopamine (DA)-containing neurons. Single-cell electrophysiological recordings were made in the substantia nigra (SN) and ventral tegmental area (VTA) of chloral hydrate anesthetized rats. In this post-weaning exposure protocol 22-day-old male Sprague-Dawley rats were exposed to Pb- (100, 250, and 500 ppm) or Na-acetate in the drinking water for a period ranging from 3 to 6 weeks. Animals were exposed up to the day of electrophysiological recording. One Pb- and one Na-treated animal were recorded each experimental day. The post-weaning exposure protocol used in this study resulted in a significant Pb-dependent decrease in the number of spontaneously active DA neurons at the time of electrophysiological recording. Analysis of covariance, using duration of exposure as the covariate (i.e. 3, 4, 5, or 6 weeks), did not indicate that there was a consistent relationship between exposure duration and the number of spontaneously active DA neurons. However, the effect of Pb was dependent on the level of Pb exposure through the drinking water. At the 250 and 500 ppm level of exposure, Pb produced a significant decrease in the number of spontaneously active DA neurons in both anatomical regions. The number of active DA neurons was not significantly affected by the 100 ppm Pb treatment over the 3-6 weeks exposure period. The average discharge rate, and the percentage of spontaneously active DA neurons classified as having discharge patterns with bursts (i.e. 'bursting DA neurons'), was not changed at any of the three levels of Pb exposure. Based on results obtained from electrophysiological studies, the effect of selected Pb exposure levels, 250 and 500 ppm, were examined during the postnatal period using tyrosine hydroxylase (TH) immuno-histochemistry to determine if Pb affects the survival of dopamine neurons within SN and VTA. TH immuno-histochemical studies revealed that the reduction in the number of spontaneously active DA neurons in animals treated with 250 and 500 ppm Pb was probably not related to the physical loss of cells (e.g. necrosis or apoptosis).
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy and Allied Health Professions, Wayne State University, Detroit, MI 48202, USA.
authors.forename: M
authors.initials: M
authors.lastname: Tavakoli-Nezhad
authors.forename: A J
authors.initials: AJ
authors.lastname: Barron
authors.forename: D K
authors.initials: DK
authors.lastname: Pitts
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002452:Cell Count; D016923:Cell Death / Q000187:drug effects; D004298:Dopamine / Q000502:physiology*; D004594:Electrophysiology; D007854:Lead / Q000097:blood / Q000633:toxicity*; D008297:Male; D008636:Mesencephalon / Q000473:pathology*; D009474:Neurons / Q000473:pathology*; D016627:Oxidopamine; D051381:Rats; D017207:Rats, Sprague-Dawley; D013563:Sympathectomy, Chemical; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D007854:Lead; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine