Omega-3 fatty acid deficiency augments amphetamine-induced behavioral sensitization in adult DBA/2J mice: relationship with ventral striatum dopamine concentrations.

The principal polyunsaturated fatty acid acids found in brain, arachidonic acid (AA) and docosahexaenoic acid (DHA), preferentially accumulate in synaptic membranes. Although neurochemical studies have found that dietary-induced deficits in rat brain DHA composition significantly alter mesocorticolimbic dopamine (DA) neurotransmission, its impact on DA-mediated behavior remains poorly understood. In the present study, we determined the effects of dietary-induced deficits in brain DHA composition on amphetamine (AMPH)-induced locomotor activity and sensitization in DBA/2J mice, an inbred strain previously found to be hyporesponsive to AMPH, as well as monoamine concentrations in the PFC and ventral striatum following the AMPH challenge. Chronic dietary omega-3 fatty acid deficiency significantly decreased PFC (-25%) and ventral striatum (-20%) DHA composition, increased PFC (+7%) and ventral striatum (+6%) AA composition, and increased the AA:DHA ratio in PFC (+30%) and ventral striatum (+24%). The development and expression of AMPH-induced sensitization was significantly increased in DHA-deficient mice, whereas novelty- and acute AMPH-induced locomotor activity were not altered. DHA-deficient mice exhibited significantly greater ventral striatum, but not PFC, DA and DA metabolite concentrations following the AMPH challenge, whereas serotonin and noradrenalin concentrations were not altered. Ventral striatum AA composition and the AA:DHA ratio were both positively correlated with DA concentrations, and both ventral striatum AA composition and DA concentrations were positively correlated with locomotor activity during the preceding AMPH challenge. These results demonstrate that dietary-induced brain DHA deficiency, and associated elevation in the AA:DHA ratio, augment AMPH-induced sensitization in DBA/2J mice, and that this augmented response is associated with selective alterations in the mesolimbic DA pathway.