Neonatal nicotine exposure impairs development of auditory temporal processing

Abstract

Accurate temporal processing of sound is essential for detecting word structures in speech. Maternal smoking affects speech processing in newborns and may influence child language development; however, it is unclear how neonatal exposure to nicotine, present in cigarettes, affects the normal development of temporal processing. The present study used the gap-induced prepulse inhibition (gap-PPI) of the acoustic startle response to investigate the effects of neonatal nicotine exposure on the normal development of gap detection, a behavioral testing procedure of auditory temporal resolution. Neonatal rats were injected twice per day with saline (control), 1mg/kg nicotine (N-1 mg) or 5 mg/kg nicotine (N-5 mg) from postnatal day 8-12 (P8-P12). During the first month after birth, rats showed poor gap-PPI in all three groups. At P45 and P60, gap-PPI in control rats improved significantly, whereas rats exposed to nicotine exhibited less improvement. At P60, the gap-detection threshold in the N-5 mg group was significantly higher than in the control group, suggesting that neonatal nicotine exposure affects the normal development of gap-detection acuity. Additionally, 1h after receiving an acute nicotine injection (1 mg/kg), gap-PPI recorded in adult rats from the N-5 mg group showed a temporary significant improvement. These results suggest that neonatal nicotine exposure reduces gap-PPI implying an impairment of the normal development of auditory temporal processing by inducing changes in cholinergic systems.

Figure 1

Prepulse inhibition paradigm used to record gap detection and noise-burst induced prepulse inhibition. (A) The acoustic startle response was recorded from rats elicited by a white noise burst presented at 100 dB SPL for 20 ms. (B) A gap (ranging from 1 to 100 ms) embedded in a continuous white noise (60 dB SPL) 60 ms prior to the startle acoustic signal inhibits the startle response by reducing the amplitude. This inhibition is defined as gap-PPI. (C–D) A narrow-band noise (NBN) burst (60 dB SPL, 20 ms) 60 ms prior to the startle eliciting sound induced inhibition on the startle reflex amplitude defined as NB-PPI. STng: startle reflex elicited by an acoustic stimulus in continuous noise without a preceding gap; STg: startle reflex elicited by an acoustic stimulus in continuous noise with a preceding gap; STq: startle reflex elicited by an acoustic stimulus without a preceding stimulus; STnb: startle reflex elicited by an acoustic stimulus with a preceding narrow band noise.

Figure 2

Effects of neonatal nicotine exposure on the developmental change of gap detection. At P20 and P28, gap-PPI showed no difference between the nicotine exposed groups (N-1mg and N-5mg) and the saline group (A, B). At P35, gap-PPI recorded in the N-5mg group was slightly but not significantly smaller than in the saline and the N-1mg groups (C). At P45 and P60, the gap-induced PPI was significantly lower than in the N-1mg group and the saline group (D, E). Rats in the N-5mg group showed a significantly elevated gap detection threshold compared to the N-1mg and the saline group (F) (* P<0.05, ** P<0.01).

Figure 3

(A) Neonatal nicotine exposure did not show any significant effects on the narrowband noise induced pre-pulse inhibition of startle response (NB-PPI). (B) ABR thresholds recorded from neonatal nicotine exposed rats were slightly lower than saline treated rats (Student’s t-test, * P<0.05).

Figure 4

Effects of acute nicotine treatment (1 mg/kg) on the gap-induced prepulse inhibition of startle reflex (gap-PPI) in adult rats. (A) Nicotine improved gap-PPI recorded from N-5mg group. (B) One hour after nicotine treatment, gap-detection thresholds was significantly decreased. After 4 days, the acute changes had disappeared, ruling out permanent changes caused by acute nicotine treatment. The nicotine treatment on the saline group showed a slight enhancement on gap-PPI (C), but did not show a significant change on gap detection threshold (D) (* P<0.05).

Figure 5

Effects of acute nicotine treatment (1 mg/kg) on the noise-burst induced prepulse inhibition of the startle reflex (NB-PPI) at P60. (A) NB-PPI was increased after the nicotine treatment recorded from N-5mg group. This enhancement had disappeared after 4 days. (B) The nicotine treatment on the saline group did not show any significant changes on NB-PPI (* P<0.05).