[Effects of acrylamide on rat neurobehavior, the contents of dopamine and its metabolites in nigrostriatal dopaminergic pathways].

OBJECTIVE: To explore the neurotoxic effect of acrylamide on nigrostriatal dopaminergic pathways in male SD rats and its mechanism. METHODS: Fourteen male SD rats were randomly divided into 2 groups: control group, and ACR exposed group (40 mg/kg). Exposed SD rats were intragastrically administrated acrylamide (40 mg/kg) once daily for 12 days, the control rats were only administrated with normal saline by gavage. Neurobehavioral indexes including body weight, gait scores, nervous sensory to heat, foot splay in hindlimb landing were measured, then the contents of dopamine (DA) and its metabolites, 3, 4-dihydroxyphenylacetic acid (DOPAC) and homovanilic acid (HVA) in the striatum were analyzed by HPLC-fluorescence detection. RESULTS: In comparison with control, there were significant differences in all neurobehavioral indexes (P < 0.05). The contents of DA in ACR exposed group decreased by 65.64% compared with the control group (P < 0.05). However, no significant differences of DOPAC and HVA content were found between ACR exposed group and control group. CONCLUSION: Acrylamide may affect neurobehavior of rats and decrease the level of dopamine in striatum, thus induce a series of neurotoxic effects.

Acrylamide increases dopamine levels by affecting dopamine transport and metabolism related genes in the striatal dopaminergic system.

Dopaminergic system dysfunction is proved to be a possible mechanism in acrylamide (ACR) -induced neurotoxicity. The neurotransmitter dopamine (DA) has an increasingly important role in the dopaminergic system. Thus, the goal of this study is to evaluate effects of ACR on dopamine and its metabolite levels, dopamine transport and metabolic gene expression in dopaminergic neurons. Male Sprague-Dawley (SD) rats were dosed orally with ACR at 0 (saline), 20, 30, and 40 mg/kg/day for 20 days. Splayed hind limbs, reduced tail flick time and abnormal gait which preceded other neurologic parameters were observed in the above rats. ACR significantly increased dopamine levels, decreased 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanilic acid (HVA) contents in an area dependent manner in rat striatum. Immunohistochemical staining of the striatum revealed that the number of tyrosine hydroxylase (TH) positive cells significantly increased, while monoamine oxidase (MAO) positive cells were drastically reduced, which was consistent with changes in their mRNA and protein expressions. In addition, dopamine transporter (DAT) and vesicular monoamine transporter 2 (VMAT2) expression levels were both down-regulated in the striatum. These results suggest that dopamine levels increase significantly in response to ACR, presumably due to changes in the dopamine transport and metabolism related genes expression in the striatal dopaminergic neurons.