Several studies in rodents have suggested the inactivation of the subthalamic nucleus (STN) as an alternative strategy to Parkinson's disease (PD) treatment. The STN is part of the basal ganglia and plays an important role in the motor function; however, recent data suggest that this structure has a critical role in the cognitive function of the limbic system. The STN receives direct projection from the prefrontal cortex (PFC), structure interconnected with the hippocampus and both structures send excitatory projections to the nucleus accumbens (NAcc). Here, we determined whether and which changes occurred 4 weeks after a STN lesion in the dendritic morphology of pyramidal neurons of the layers 3 and 5 of the PFC and basolateral amygdala, neurons of the ventral hippocampus, and the medium spiny neurons of the NAcc and caudate-putamen. Dendritic morphology was measured using the Golgi-Cox procedure followed by Sholl analysis. We also evaluated the effects of STN lesion on locomotor behavior assessed by an open field test, social interaction, acoustic startle response, prepulse inhibition, and locomotor activity induced by a novel environment and amphetamine. We found that STN damage induced a deficit in locomotion measured by open field test with neuronal hypertrophy in PFC (layer 5) and reduced spinogenesis in CA1 ventral hippocampus and PFC (layer 3). Taken together, these data suggest that the behavioral and morphological effects of STN lesion are, at least partially, mediated by limbic subregions with possible consequences for cognitive-related behaviors observed in PD treatment. Synapse 68:114–126, 2014. © 2013 Wiley Periodicals, Inc.