Chronic alcohol consumption impairs visuo-spatial associative memory in periadolescent rhesus monkeys

Abstract

Alcohol abuse in the adult is often preceded by high alcohol consumption during adolescence. Profound changes in brain structure and function occur during this developmental period, therefore alcohol may impact essential cognitive skill development during the formal educational years. The objective of this study was to determine if chronic oral alcohol intake slows acquisition and performance of cognitive tasks in male adolescent rhesus monkeys. Treatment groups (Alcohol, N=4; Control, N=3) were evaluated on bimanual dexterity and tests of visuo-spatial memory and learning adapted from the Cambridge Neuropsychological Test Automated Battery. Animals were trained daily in 30 min sessions and had subsequent access to alcohol/Tang® solutions (Alcohol group) or Tang® only (Control group) Monday through Friday for 11 months. Recordings of brainstem auditory evoked potentials (BSAEP) were conducted periodically before and during the chronic drinking.

Results: Chronic alcohol drinking (ave of 1.78 g/kg alcohol per session) impaired behavioral performance assessed ∼22 h after the prior drinking session. The Alcohol group required more trials than the Control group to reach criterion on the visuo-spatial memory task and showed increased sensitivity to trial difficulty and retention interval. Alcohol animals also had slowed initial acquisition of the bimanual task. The latency of P4 and P5 BSAEP peaks were also delayed in the Alcohol group. Chronic alcohol consumption impaired the acquisition and performance of a spatial memory task and disrupted brainstem auditory processing, thus these results show that repeated alcohol exposure in adolescence interferes with a range of brain functions including complex visuo-spatial mnemonic processing.

Figure 1

A) Mean (N=7; ±SEM) ethanol (EtOH) intake during the induction phase. B) Individual animals’ mean EtOH intake for the final 6 sessions of induction during which 2.0 g/kg was made available. Individuals are grouped by subsequent treatment assignment. C) Mean (N=4; ±SEM) daily EtOH consumption over 90 sessions of EtOH maintenance conducted over about 5 months. Data are presented as sequential 5-session averages and a gap in the series indicates when one individual was briefly discontinued from EtOH access for health reasons unrelated to EtOH drinking. D) Blood EtOH levels for all monkeys after sessions (1 mo and 10 mo after the start of chronic exposure) in which 3.0 g/kg was made available. This is a modification of Figure 1 from a prior publication (Taffe et al. 2010).

Figure 2

A) Touch accuracy during the initial touch-screen training, prior to any EtOH exposure, is presented for the eventual Alcohol (N=4) and Control (N=3) groups. B) Performance on the Intradimensional / Extradimensional Attentional Set Shift task, conducted prior to EtOH exposure, is presented for the eventual treatment groups. Data are presented as a square root transformation of errors-to-criterion. Simple Discrimination, SD; Simple Discrimination Reversal, SR; Compound Discrimination, CD; Compound Discrimination Reversal, CR; Intradimensional Shift, IDS; Intradimensional Shift Reversal, IDR; Extradimensional Shift, EDS; Extradimensional Shift Reversal, EDR. A significant difference between pairs of acquisition and reversal stages (SD/SR, CD/CR, IDS/IDR, EDS/EDR) within treatment group is indicated by *. Bars indicate SEM in both panels.

Figure 3

A) The mean number of training sessions required to meet acquisition criteria for the visuo-spatial Paired Associates Learning task is presented for the Alcohol (N=4) and Control (N=3) groups. Mean accuracy for B) the 1-stim (2-loc) and C) the 1-stim (3-loc) trials are presented for the Alcohol (N=4) and Control groups (N=3).) A significant difference in performance from the first block of 5 training sessions is indicated by * and the # indicates a significant difference between treatment groups. Other symbols reflect a significant increase (&) or decrease (§) relative to performance on the 1-stim (2-loc) trials for a given block of training sessions. Bars indicate the SEM in all panels.

Figure 4

Mean percent correct trials on the initial attempt, as well as after up to 5 additional repeated attempts to complete the trial, are given for the Alcohol (N=4) and Control groups (N=3); bars indicate SEM. A significant difference from performance on the easiest trial type (1, 2: 1 stimulus (2 locations)) is indicated by * and the § indicates significantly improved performance between the initial attempt and after up to 5 additional repeated attempts.

Figure 5

Mean choice accuracy in the spatial delayed-response probe is presented for Alcohol (N=4; ±SEM) and Control (N=3; ±SEM) groups. A significant decrease relative to the 1 second retention interval condition is indicated by * and a # indicates a significant difference between the groups.

Figure 6

The mean time required to retrieve 15 raisins in the bimanual motor skill task is presented for the Alcohol group (N=4) and Control groups (N=3) under initial training (the raisins are partially extended for the first 5 sessions) and standard (sessions 10–20) conditions.

Figure 7

The mean (±SEM) latencies for the P4 and P5 peaks of the brainstem auditory evoked potentials (BSAEP) are presented for the Alcohol (N=4) and Control (N=3) monkeys. Recordings were conducted before alcohol exposure (baseline) and periodically in the months during chronic alcohol exposure. A significant difference from baseline within a treatment group is indicated by * and the # indicates a significant difference between treatment groups.