Event-related potential responses to the acute and chronic effects of alcohol in adolescent and adult Wistar rats

Abstract

Background: This study explored the hypothesis that adolescent ethanol (EtOH) exposure may cause long-lasting changes in EtOH sensitivity by exploring the age-related effects of acute alcohol on intoxication and on event-related potential (ERP) responses to acoustic stimuli in EtOH-naïve adolescent and adult male Wistar rats and in adult rats that were exposed to chronic EtOH/control conditions during adolescence.

Methods: EtOH-naïve adolescent (postnatal day 32 [PD32]) and adult male rats (PD99) were included in the first study. In a second study, rats were exposed to 5 weeks of EtOH vapor (blood EtOH concentrations at 175 mg%) or air from PD24 to 59 and allowed to mature until PD90. In both studies, rats were implanted with cortical recording electrodes, and the effects of acute EtOH (0.0, 1.5, and 3.0 g/kg) on behavioral and ERP responses were assessed.

Results: Adolescents were found to have higher amplitude and longer latency P3a and P3b components at baseline as compared to adult rats, and EtOH was found to produce a robust dose-dependent increase in the latency of the P3a and P3b components of the auditory ERP recorded in cortical sites in both adolescents and adults. However, EtOH produced significantly larger delays in P3a and P3b latencies in adults as compared to adolescents. Acute EtOH administration was also found to produce a robust dose-dependent increase in the latency of the P3a and P3b components in adult animals exposed to EtOH vapor as adolescents and air exposed controls; however, larger acute EtOH-induced increases in P3a and P3b latencies were seen in controls as compared to adolescent vapor exposed rats.

Conclusions: Adolescent rats have a less intense P3 latency response to acute EtOH administration when compared to adult rats. Exposure to chronic EtOH during adolescence can cause "retention" of the adolescent phenotype of reduced P3 latency sensitivity to EtOH.

Keywords: Adolescence; Alcohol; Ethanol; Event-Related Potentials; P300; Tolerance.

Figure 1

Experimental timeline for study 2. Weights and BAL's shown over time for the adolescent vapor exposed rats (N=24) and their controls (N=20). Significant events and durations are shown, all electrophysiological data collected between PD99 and PD124.

Figure 2

Representative ERP waveforms of an adolescent and adult rat from study 1. Approximate locations for N1, P2, P3a and P3b are indicated on each waveform.

Figure 3

Grand averages of ERP waveforms in the FCTX and PCTX for adolescent (N=18) and adult (N=17) rats from study 1. Each acute ethanol dose is overlaid for each channel and approximate locations for P3a and P3b indicated for the saline dose. (A) Adolescent rats have much greater amplitude overall compared to (B) adults, while dose dependent changes in latency can be seen in both age groups.

Figure 4

P3a and P3b component analysis between adolescent (N=18) and adult (N=17) rats given acute ethanol. (A) Latency of the P3a and P3b component was observed to be significantly longer in adolescents compared to adults, and while both showed an ethanol dose dependent increase in latency, adults produced larger increases by dose compared to adolescents in both electrode locations. Post-hoc analyses showed that the 1.5 g/kg and 3.0 g/kg ethanol dose were significant in P3a and P3b at both electrode locations. (B) P3a and P3b amplitudes were significantly higher in adolescent rats compared to adults, but no group x dose effects were seen. * = dose effect; † = group effect; ¥ = group x dose interaction.

Figure 5

Grand averages of ERP waveforms in the FCTX and PCTX for adolescent vapor exposed rats (N=18) and their air exposed controls (N=17) rats from study 2. Each acute ethanol dose is overlaid for each channel and approximate locations for P3a and P3b indicated for the saline dose. Ethanol dose dependent effects can be seen in both (A) adolescent vapor exposed rats and their (B) controls.

Figure 6

P3a and P3b component analysis between adolescent vapor exposed rats (N=18) and air exposed controls (N=34) rats given acute ethanol. Dose dependant increases can be seen in (A) latency for both the P3a and P3b components in both electrode locations. Additionally, treatment x dose interaction show control rats have greater increases in latency compared to rats exposed to vapor during adolescence. Post-hoc analyses showed that the 1.5 g/kg and 3.0 g/kg ethanol dose were significant in P3a and P3b at both electrode locations. (B) No significant effects were seen in amplitude between adolescent vapor exposed rats and their controls. * = dose effect; ¥ = dose x treatment interaction.