Involvement of nigrostriatal dopaminergic system in the gnawing behaviors induced by clonidine plus muscimol in mice

The neurochemical and behavioral studies were carried out to clarify the neuronal mechanisms involved in the stereotype gnawing behaviors induced by clonidine (as an adenosine antagonist) plus muscimol (a GABA-a agonist) in mice. Combined treatment of clonidine (20mg/kg ip) and muscimol (0.5mg/kg ip) significantly increased 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) levels in the dosal striatum as compared with saline group. Conversely, DOPAC levels in the medial prefrontal cortex tended to decrease, but not significantly. There was no significant change in serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) levels among any regions. The frequency of gnawing behaviors was proportional to the dose of muscimol (0.25-1.0mg/kg), but not to that of clonidine (20-40mg/kg). Gnawing behaviors were hardly produced by muscimol (0.5mg/ kg) or clonidine (20mg/kg) alone. Haloperidol (0.1, 0.2mg/kg ip), but neither bisusulline (1.0-3.0mg/kg ip