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To investigate the psychiatric symptoms accompanying the early phases of Parkinson's disease (PD), we injected adult rats with 10.5 microg 6-hydroxydopamine (6-OHDA) bilaterally into the dorsal striatum. The resulting neurodegeneration led, 12 weeks after injection, to a mild (36%) reduction of striatal dopamine. We tested the behavioral response of sham and 6-OHDA-lesioned animals at different time points after injection to evaluate the onset and progression of behavioral abnormalities. The results showed that such a mild reduction of dopamine levels was associated with a decrease in anxiety-like behavior, an increase in "depression"-like behavior, and a marked change in social behavior. Learning and memory abilities were not affected. Overall, the PD rat model used here displays behavioral alterations having face validity with psychiatric symptoms of the pathology and thus appears to be a valuable tool for investigating the neural bases of the early phases of PD.

Early experiences affect brain function and behavior at adulthood. Being reared in a communal nest (CN), consisting of a single nest where three mothers keep their pups together and share care-giving behavior from birth to weaning (postnatal day [PND] 25), provides an highly socially stimulating environment to the developing pup. Communal nest characterizes the natural ecologic niche of many rodent species including the mouse. At adulthood, CN reared mice, compared to mice reared in standard nesting laboratory condition (SN), show an increase in BDNF protein levels and longer survival of BrdU-positive cells in the hippocampus. Open field and elevated plus maze results indicate that CN mice, although showing levels of exploratory and locomotor activity similar to those of SN mice, displayed increased anxiety-like behavior, performing more thigmotaxis in the open field and spending less time in the open arms of the plus maze. Furthermore, CN mice displayed higher levels of immobility behavior in the forced swim test. Overall, these findings show that CN, an highly stimulating early social environment, increases adult neuronal plasticity, as suggested by high BDNF levels and augmented number of newly generated cells in the hippocampus, which is associated to an increased anxiety- and "depression"-like behavior. These findings are discussed in the framework of the neurotrophin hypothesis of depression.