Environmental enrichment reverses prenatal ethanol exposure-induced attention-deficits in rats

Abstract

Introduction: There is a high prevalence of fetal alcohol spectrum disorders (FASD) in the US and the world, which is caused by prenatal ethanol exposure (PE). Most individuals with FASD show attention deficit hyperactivity disorder (ADHD) -like symptoms. Using a rat model of FASD, we have successfully demonstrated that moderate and heavy PE leads to persistent attention deficits, including augmented impulsivity and impaired sustained attention. Anxiety is another primary symptom of FASD. Anxiety and ADHD are closely associated in clinical studies. However, the causal relationship between anxiety and ADHD is not clear. In the present study, we used the strategy of environmental enrichment to reduce anxiety after PE in rats and investigated if attention deficits could be ameliorated.

Methods: A 2nd-trimester binge-drinking pattern of heavy PE was used. Environmental enrichment consisted of neonatal handling and postweaning complex housing. Action impulsivity and sustained attention were tested in adult males and females using the 2-choice reaction time task.

Results: The results show environmental enrichment effectively ameliorated action impulsivity and improved sustained attention in male and female PE rats. Action impulsivity was also improved in control rats with environmental enrichment. In addition, environmental enrichment improved the efficiency of obtaining rewards in male and female control but not PE rats. Environmental enrichment altered the pattern of reaction time components, favoring slower movement initiation but faster movement.

Discussion: These observations support that environmental enrichment could be an effective strategy in ameliorating ADHD-like symptoms in FASD. The reduced anxiety could contribute to such an effect.

Keywords: anxiety; attention deficit-hyperactivity disorder; fetal alcohol spectrum disorders; impulsivity; sustained attention.

Figure 1

The trial composition of the 2-choice reaction time (2-CRT) task. The upper panel depicts the composition of all trials (A). The lower panel depicts the portions of each trial type (B). Prenatal treatment (control; PE), postnatal rearing conditions (standard; environmental enrichment), or sex (male; female) did not impact the proportions of different trial types.

Figure 2

Environmental enrichment increased the number of trials in control and PE rats of both sexes. Rearing in the enriched environment increased the number of choice trials/sessions in control rats of both sexes but not in PE rats (A). Such an effect was more prominent in males, shown as a persistent escalation of trials soon after the session started (B). Environmental enrichment also increased the number of forced trials in male control and PE rats (C) and led to more reinforced trials in control, but not PE rats of both sexes (D). *P< 0.05, ***P< 0.001.

Figure 3

Environmental enrichment altered the reaction time (RT) pattern by increasing initiation time and decreasing movement time. The reaction time consists of two components: initiation time and movement time (A). There were no group differences in total reaction time (B). The initiation time was increased while the movement time was decreased in control and PE rats of both sexes reared in the enriched environment (C, D). *** P< 0.001.

Figure 4

Environment enrichment decreased action impulsivity measured by premature initiations in both control and PE rats. Action impulsivity was measured by premature initiations/trial during hold time. The data was analyzed at low and high cognitive loads (hold time< 4 s and hold time > 4 s). Environmental enrichment reduced premature initiations/trials in male control and PE rats at both low and high cognitive loads (A, B). Similar effects were observed in female rats (C, D). Increased premature initiations/trial were also observed in female PE compared to controls but not male rats (C, D). *P< 0.05, **P< 0.01, ***P< 0.001.

Figure 5

Environment enrichment did not alter action impulsivity measured by false alarms. Action impulsivity was measured by false alarms/trial at low and high cognitive load (hold time< 4 s and hold time > 4 s). We did not find a PE effect on rats reared in the standard condition (A-D). Environmental enrichment reduced the false alarms/trial females with low and high cognitive load (C, D). ***P< 0.001.

Figure 6

Environmental enrichment reduced trial completion time. The duration to complete each trial was analyzed at low and high cognitive load conditions (hold time< 4 s and hold time > 4 s). Environmental enrichment reduced trial completion time in male PE rats when cognitive load was low (A, B left panels) and females (C, D) control and PE rats when the cognitive load was high. **P<0.01, ***P< 0.001.

Figure 7

Environment enrichment did not impact lapses of attention reflected by incorrect responses or omissions. The percent incorrect response was increased in male PE rats reared in either standard or enriched condition (A). No other PE or environmental enrichment effect was observed (B-D).

Figure 8

Environmental enrichment reduced the deficits in lapses of attention in PE rats. Prenatal ethanol exposure led to deficits in lapses of attention, which was reflected as increased skewness in total reaction time in female PE rats (D). Environmental enrichment reduced deficits in lapses of attention reflected in total reaction time in male control and PE rats of (A) and female PE rats (D). Environmental enrichment also decreased the skewness of initiation time in PE rats of both sexes (B, E). No group differences in the skewness of movement time were found (C, F). *P< 0.05, **P< 0.01, ***P< 0.001.