Differential dopamine-mediated effects in the 5-lipoxygenase deficient mice

Abstract

Abstract The role of 5-lipoxygenase/leukotrienes on the central nervous system has been considered in both physiological end pathological states. Investigating the interaction between 5-lipoxygenase/leukotrienes and the dopaminergic system may provide better understanding of dopamine-related pathologies. This study aimed to investigate motor and non-motor dopamine-related responses in 5-lipoxygenase/leukotrienes-deficient mice. Pharmacological challenges of the dopaminergic system included amphetamine, apomorphine and reserpine treatment along with their respective effects on prepulse inhibition (PPI) response, general motor activity, and oral involuntary movements. Reserpine-treated mice were also investigated for their striatal glial markers’ expression (GFAP and Iba-1). 5-lipoxygenase/leukotrienes-deficient mice exhibited increased spontaneous locomotor activity, including horizontal and vertical exploratory activity, and stereotyped-like behavior compared to wild-type mice. This condition was attenuated by acute apomorphine treatment. Despite the absence of altered basal responses in the PPI there was a significant and selective decreased in susceptibility in amphetamine-induced PPI disruption in 5-lipoxygenase/leukotrienes-deficient mice. However, there was an increased vulnerability to reserpine-induced involuntary movements. There was no alteration in the basal expression of striatal GFAP and Iba-1 positive cells in 5-lipoxygenase/leukotrienes-deficient mice compared to wild-type mice. Reserpine treatment induced a significant increase in GFAP immunoreactivity in wild-type mice but this effect was absent in the 5-lipoxygenase deficient mice. The percentage of activated microglia was found to be significantly increased in reserpine-treated wild-type mice. This effect was absent in the 5-lipoxygenase/leukotrienes-deficient mice. Our results support the conception of a unique dopaminergic pathway phenotype in 5-lipoxygenase/leukotrienes-deficient mice. These findings suggest that leukotrienes may interfere with the orchestration of dopamine-mediated responses.