Postnatal inorganic lead exposure decreases the number of spontaneously active midbrain dopamine neurons in the rat.

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).

Effects of chronic low-level oral lead exposure on prepulse inhibition of acoustic startle in the rat.

Previous work has suggested that the behavioral effects of chronic low-level lead exposure on fixed interval (FI) operant behavior result from enhanced dopaminergic neurotransmission in the nucleus accumbens (Cory-Slechta et al., J Pharmacol Exp Ther 286: 794-805, 1998). The present studies were designed to further characterize the effects of chronic low-level oral lead exposure on another behavior that is modulated by dopaminergic neurotransmission in the nucleus accumbens. In these studies acoustic startle and the prepulse inhibition (PPI) of startle were studied in rats following chronic low-level oral lead exposure. Weanling male rats were treated for 5-6 weeks with lead via drinking water (250 ppm lead acetate; controls drank 250 ppm sodium acetate). Acoustic startle reactivity (95, 105, and 115 dB noise bursts) and PPI (prepulses of 1-8 dB over the 70-dB background) of startle were tested following lead exposure. Lead exposure did not affect body weight. Lead exposure also did not significantly affect baseline [i.e., no prepulse inhibition (NO-PPI)] acoustic startle as measured by 1) startle amplitude on the first startle trial (105 dB), 2) the average startle amplitude for the first ten trials (105 dB), or 3) the average startle amplitude for the NO-PPI trials during PPI testing (95, 105, and 115 dB). Lead exposure also did not affect the latency to onset for the startle response. In contrast, for both the 105 dB and 115 dB acoustic startle stimuli, chronic low-level oral lead exposure significantly attenuated the capacity of an acoustic prepulse to reduce the startle response. This effect was present whether the data were presented and analyzed as raw change from baseline or as the percentage of baseline startle. Given the strong link between the modulation of PPI and dopaminergic neurotransmission in the nucleus accumbens, the present data support the hypothesis that chronic low-level oral lead exposure facilitates dopamine neurotransmission in the nucleus accumbens.