Behavioral effects of intra-nigral microinjections of manganese chloride: interaction with nitric oxide.

ABSTRACT

1. Microinjection of manganese chloride (MnCl2) into the rat substantia nigra pars compacta (SNc) induces a neurodegenerative process manifested by apomorphine-induced rotational behavior. Manganese intoxication produces a parkinsonism-like phenotype in humans. 2. In addition to motor control the substantia nigra has also been proposed to be related to epilepsy and emotional behavior. 3. Although nitric oxide (NO) participation in neurodegenerative processes is still questioned, neurons stained for NAPDH-diaphorase, a marker of NO-producing cells, are spared in several experimental neuronal lesions. Additionally, NO has also been suggested to participate in motor control. 4. The objective of this study was to analyze the effects of MnCl2-induced nigral degeneration in audiogenic seizure susceptibility, anxiety and motor activity. We also analyzed if NO synthesis inhibition (N(G)-nitro-L-arginine 25 mg/Kg twice a day for 4 days) modifies MnCl2-induced neurodegenerative process. 5. MnCl2 (50 microg) microinjection into the SNc caused a statistical significant higher number of apomorphine (0.75 mg/kg s.c.)-induced rotations. No sensitization to audiogenic seizure was found but the lesion induced an increase of open arm exploration in the elevated plus maze, suggesting an anxiolytic effect. 6. The MnCl2-nigral lesion was accompanied by an increased number of NADPH-d positive neurons in the ipsilateral SNc and striatum (both sides). NO synthesis inhibition potentiated the MnCl2-nigral lesion and reversed the NADPH-d cell number increase. 7. The present results show that MnCl2-nigral lesion can influence emotional behavior and suggest that NO may modify the progression of manganese-induced degenerative process.