Mattsson A, Lindqvist E, Ögren SO, Olson L (2002) Amphetamine hyperresponses in cholinergically denervated rats and alpha7 nAChR knockout mice, and effects of nicotinic agonists. Neuroscience 2002 Abstracts 136.7. Society for Neuroscience, Orlando, FL.
Summary: We have recently shown that cholinergic denervation of the basal forebrain in adult rats, using intracerebroventricular injections of the cholinergic immunotoxin 192-saporin, leads to overreactivity in dopaminergic systems, in the form of enhanced amphetamine-induced hyperactivity. This increased sensitivity to amphetamine in cholinergically denervated rats can be partially counteracted by nicotine if given before the amphetamine challenge. The results provide a possible link between deficits in central cholinergic systems and overactivity in dopaminergic systems, which might be of relevance for the pathogenesis of schizophrenia. To further evaluate the role of cholinergic dysfunction for dopaminergic hyperactivity we have focused on the α7 nAChR due to its presumed involvement in schizophrenia. First, we tested if a selective α7 nAChR agonist, AR-R17779, could mimic the effect of nicotine (partial blockade of amphetamine hyperresponse) in cholinergically denervated rats. Second, we tested if mice lacking the α7 nAChR gene have a similar increased sensitivity to amphetamine, as cholinergically denervated rats. Preliminary results from these studies show that AR-R17779 normalizes the effect of amphetamine cholinergically denervated rats, and further, that lack of the α7 nAChR gene leads to an increased sensitivity to amphetamine. Cholinergic deficiencies that cause dopaminergic overactivity are compatible with a role of the α7 nAChR in schizophrenia and may suggest a role for the cholinergic system in other psychotic states.
Related Products: 192-IgG-SAP (Cat. #IT-01)