Decreased brain docosahexaenoic acid during development alters dopamine-related behaviors in adult rats that are differentially affected by dietary remediation.

Docosahexaenoic acid (DHA) is a major component of neuronal membranes. In rats, low brain levels of DHA during development produce alterations in the mesocortical and mesolimbic dopamine systems. In this study, male Long-Evans rats (n = 6-7 per group) were raised from conception on diets with (control) or without alpha-linolenic acid, the dietary precursor of DHA. The deficient diet reduced brain DHA to 80% of that of control animals at maturity. At weaning (P21), half of the pups from each deficient litter were changed to a remediation diet enriched in DHA by the addition of fish oil. Beginning at P56, rats were subjected to a battery of behavioral tests. Catalepsy induced by haloperidol (3mg/kg, i.p.) in deficient animals was 49% of that observed in control animals (P < 0.05). Catalepsy in remediated animals was similar to that observed for control animals. In a test of locomotor activity in a novel environment, deficient animals exhibited 187% of the activity of control animals (P < 0.05). Locomotor activity stimulated by d-amphetamine (0.5mg/kg, s.c.) in deficient animals was 145% of that observed in control animals (P < 0.05). Basal and amphetamine-stimulated activity of remediated animals was similar to that of deficient animals. Response to a thermal stimulus was not different between groups. These findings demonstrate that rats exposed from conception to a diet that produces a relatively modest decrease in brain DHA content exhibit alterations in adult behavior indicative of altered dopaminergic function. Some of these behavioral alterations were reversed by dietary remediation initiated at weaning.