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.