Laplante FP, Dufresne M, Lappi DA, Sullivan RM (2009) Depletion of cholinergic neurons in the nucleus accumbens impairs dopamine function in the prefrontal cortex in the rat. Neuroscience 2009 Abstracts 341.7/O16. Society for Neuroscience, Chicago, IL.
Summary: Studies of post mortem schizophrenic brains have revealed a selective loss of cholinergic interneurons, most pronounced in the ventral striatal region. We have previously shown in the rat, that a novel saporin immunotoxin coupled with an antibody targeting choline acetyltransferase (ChAT) and microinjected (0.5 _g/_l; 0.5 _l) into the nucleus accumbens (N. Acc) of adult rats, reduces the number of cholinergic neurons in N. Acc. by 40-50 %. Such lesions result in a markedly heightened response to the locomotor activating effects of amphetamine and impair prepulse inhibition of the acoustic startle response. We proposed that this local cholinergic deficit leads to a hyperresponsiveness in subcortical dopamine (DA) systems of relevance to schizophrenic symptomatology. Presently, we hypothesize that the same local cholinergic defect may trigger broader changes in cortical/subcortical networks, specifically prefrontal cortex (PFC) deficits in DA-mediated functions, also proposed in schizophrenia. Young adult male Srpague-Dawley rats were injected bilaterally in the N. Acc. as described above with either the cholinergic immunotoxin or vehicle. Two weeks later, they were trained in a working memory task dependent on PFC function, using the delayed alternation paradigm in the T-maze. Lesioned rats took significantly longer to reach criterion performance during training than controls. During testing, lesioned rats were significantly impaired in the percentage of correct arm choices across delay intervals, but especially with longer (40 sec) delays. The same animals were then implanted with voltammetric recording electrodes in the ventromedial PFC to examine the increases in in vivo extracellular DA release in response to a brief tail pinch stress. Lesioned rats showed a significantly reduced activation of the mesocortical DA system compared to controls. Taken together, the data suggest that reduction in the density of cholinergic neurons in the N. Acc also triggers deficits in prefontally-mediated function known to be under mesocortical DAergic regulation. This raises the possibility that ventral striatal cholinergic deficits may be causally linked to cortical/subcortical functional imbalances proposed to exist in schizophrenia.
Related Products: Anti-ChAT-SAP (Cat. #IT-42)