Regulatory behaviour, exploration and locomotion following NMDA or 6-OHDA lesions in the rat nucleus accumbens

The effects of bilateral, N-methyl-d-aspartate (NMDA)-induced lesions of the nucleus accumbens (N.Acc.) on regulatory and behavioural responding were studied in rats and compared with the effects of bilateral 6-hydroxydopamine (6-OHDA) lesions. After postoperative body weight, food and water intake had been monitored for a period of 4 weeks, rats were tested in an exploration-choice box. Spontaneous locomotion and the locomotor and stereotypy responses to different doses of dopaminergic agonists were measured subsequently. Detailed assessment of NMDA-induced lesion volumes showed that on average 81.53% of total N.Acc. area was damaged, depending on excitotoxin dose. Tyrosine hydroxylase immunohistochemistry was used to confirm loss of mesolimbic dopamine neurones following 6-OHDA. Analysis of the behavioural data showed that NMDA N.Acc. lesions significantly enhanced exploratory behaviour, spontaneous locomotor activity and the locomotor response to a low dose of d-amphetamine. By comparison, 6-OHDA lesions did not affect exploration and spontaneous locomotion but significantly attenuated the locomotor response to a low dose of d-amphetamine. Regulatory responses were unaffected 28 days after surgery, although NMDA-lesioned rats took longer to recover from postoperative hypodipsia. The results suggest that NMDA N.Acc. lesions induce a deficit in the control of general locomotor output and are consistent with the hypothesis that the N.Acc. functions as an interface between sensory input and locomotor output and that it is needed to channel activity levels appropriately.