Subacute manganese exposure in rats is a neurochemical model of early manganese toxicity

• Systemic Mn exposure in rats produces alterations in brain catecholamines.
• Behavioral deficits in Mn-exposed rats occur as early as 8 days after exposure.
• Limited changes in other neurotransmitter systems were detected in Mn-exposed rats.

Manganese (Mn) is an essential trace element, but excess exposure leads to accumulation in biological tissues, including the brain. Chronically high Mn levels in the brain are neurotoxic and can result in a progressive, irreversible neurological disorder known as manganism. Manganism has signs and symptoms similar to, but distinguishable from idiopathic Parkinson's disease, which include both psychological and motor disturbances. Evidence suggests that Mn exposure impacts neurotransmitter levels in the brain. However, it remains unclear if subacute, low-level Mn exposure resulted in alterations in neurotransmitter systems with concomitant behavioral deficits. The current study used high performance liquid chromatography to quantify neurotransmitter levels in rat striatum (STR), substantia nigra (SN), and hippocampus (HP). Subacute Mn exposure via i.p. injection of 15 mg Mn/kg as MnCl2 caused significantly increased dopamine (DA) levels in the STR. The enhancement was accompanied by significantly elevated levels of the DA metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), in the STR. In addition, levels of HVA were significantly increased in the SN and HP. These data indicate that subacute, low-level Mn exposure disrupts multiple neurotransmitter systems in the rat brain which may be responsible, in part, for observed locomotor deficits.