Partial lesion of the dopaminergic innervation of the ventral striatum induces depressive-like behavior of rats

Depression is a frequent comorbid disorder in parkinson's disease (pd) which may precede appearance of its motor symptoms by several years. pathomechanisms underlying pd have been suggested to be responsible for the pd-related depression. the aim of the study was to examine the influence of a partial lesion of striatal dopaminergic terminals on the depressive- like behavior of rats in the forced swimming test (fs). 6-hydroxydopamine (6-ohda) was injected bilaterally into the ventro-lateral region of the caudate-putamen (cp) (3.75 μg/2.5 μl/side). the locomotor activity and behavior of rats in the fs were measured 2 and 4 weeks after the operation. the lesion extent was analyzed by biochemical and immunohistochemical methods. two weeks after the operation,the 6-ohda-treated rats displayed a prolonged immobility in the fs. this effect disappeared after 4 weeks. the locomotor activity was not influenced by 6-ohda. levels of dopamine,dopac and hvawere decreased in the nucleus accumbens (nac) 2 weeks after 6-ohda but were not changed in the cp,frontal cortex (fcx) and substantia nigra (sn). no significant effect of 6-ohda on tyrosine hydroxylase-immunoreactivity in the cp and nac were found. the present study indicates that a relatively small lesion of dopaminergic terminals in the ventral striatum,which does not produce any motor disturbances,may induce depressive-like symptoms. copyright © 2011 by institute of pharmacology polish academy of sciences.