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

1. Microinjection of manganese chloride (MnCl2) into the rat substantia nig ra pars compacta (SNc) induces a neurodegenerative process manifested by ap omorphine-induced rotational behavior. Manganese intoxication produces a pa rkinsonism-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-p roducing cells, are spared in several experimental neuronal lesions. Additi onally, 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-arginin e 25 mg/Kg twice a day for 4 days) modifies MnCl2 induced neurodegenerative process. 5. MnCl2 (50 mu g) microinjection into the SNc caused a statistical signifi cant higher number of apomorphine (0.75 mg/kg s.c.)-induced rotations. No s ensitization to audiogenic seizure was found but the lesion induced an incr ease of open arm exploration in the elevated plus maze, suggesting an anxio lytic 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 syn thesis inhibition potentiated the MnCl2-nigral lesion and reversed the NADP H-d cell number increase. 7. The present results show that MnCl2-nigral les ion can influence emotional behavior and suggest that NO may modify the pro gression of manganese-induced degenerative process.