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.
Levant
Beth
B
Department of Pharmacology, Toxicology, and Therapeutics, University of Kansas Medical Center, Mail Stop 1018, 3901 Rainbow Blvd., Kansas City, KS 66160, USA. blevant@kumc.edu
Radel
Jeffery D
JD
Carlson
Susan E
SE
D000661:Amphetamine / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal; D001835:Body Weight / Q000502:physiology; D001921:Brain / Q000254:growth & development / Q000378:metabolism*; D001923:Brain Chemistry; D002375:Catalepsy / Q000139:chemically induced / Q000503:physiopathology; D004041:Dietary Fats / Q000008:administration & dosage*; D004281:Docosahexaenoic Acids / Q000378:metabolism*; D004298:Dopamine / Q000502:physiology*; D005227:Fatty Acids / Q000032:analysis; D005260:Female; D005395:Fish Oils / Q000008:administration & dosage; D006220:Haloperidol; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D010147:Pain Measurement; D011247:Pregnancy; D051381:Rats; D020318:Rats, Long-Evans; D013997:Time Factors
D004041:Dietary Fats; D005227:Fatty Acids; D005395:Fish Oils; D004281:Docosahexaenoic Acids; D000661:Amphetamine; D006220:Haloperidol; D004298:Dopamine