title: The Effect of Dietary Polyunsaturated Fatty Acids and Alcohol on Neurotransmitter Levels in Rat Brain.
abstract: A novel animal model of alcoholism is presented which includes the features of chronic alcohol exposure, repeated withdrawal and a diet limited in essential fatty acids. The model was used to study the effect of these variables on neurotransmitter and theirmetabolites (serotonin, 5-hydroxyindole-3-acetic acid, dopamine, norepinephrine and di-hydroxyphenylacetic acid) concentrations in the brainstem, caudate, cerebellum, cortex and hippocampus of Long-Evans rats. Two novel, nutritionally adequate liquid diet compositions were developed using elements of the AIN-93M and Lieber-DeCarli rodent diets. The basal diet bad low (0.3 en%) levels of the essential fatty acids 18: 2n6 and 18: 3n3 (BASE). The experimental diet (PUFA) was identical to BASE except for the addition of low levels, 0.5 en% each, of arachidonic acid (AA) and docosahexaenoic acid (DHA). Animals on ethanol (EtOH) containing diets (BASE-EtOH and PUFA-EtOH) experienced eight intermittent ethanol withdrawal periods during the three month exposure period. One group of rats were on a continuous alcohol regime (BASE-EtOH(cont.)) with a single withdrawal period at the end of the study. Using the isocaloric pair-feeding technique for liquid diets, the effects of diet, alcohol and withdrawal were studied in 69 (44 were used for neurotransmitter determinations) individually housed rats over ninety days. Neurotransmitter levels were generally higher in the BASE and PUFA groups compared to BASE-EtOH and PUFA-EtOH, respectively. The concentrations of the serotonin metabolite 5-hydroxyindole-3-acetic acid were reduced in all five areas in the brain of the BASE-EtOH animals, given multiple withdrawal periods in comparison to the BASE-EtOH(cont.) group which were administered alcohol in a continuous fashion. Long-chain PUFA, at 1.0 en%, could generally not prevent the neurotransmitter lowering effect of alcohol, but it led to an elevation of these levels in PUFA animals compared with BASE. These results indicate that dietary fatty acids influence neurotransmitter metabolism in the brain.
authors.affiliation: a Laboratory of Membrane Biochemistry and Biophysics , NIAAA, National Institutes of Health , 12420 Parklawn Drive, Room 158, Rockville , MD 20852 , USA.
authors.forename: N U
authors.initials: NU
authors.lastname: Olsson
authors.affiliation: b Laboratory of Clinical Studies, Section of Pharmacokinetic Studies , NIAAA, National Institutes of Health , Bethesda, MD , USA.
authors.forename: S E
authors.initials: SE
authors.lastname: Shoaf
authors.affiliation: a Laboratory of Membrane Biochemistry and Biophysics , NIAAA, National Institutes of Health , 12420 Parklawn Drive, Room 158, Rockville , MD 20852 , USA.
authors.forename: N
authors.initials: N
authors.lastname: Salem
keywords: Alcohol; Arachidonic acid; Docosahexaenoic acid; Liquid diet; Long-Evans rat; Neurotransmitters; Pair-feeding; Withdrawal