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Cortical cholinergic deficiency enhances amphetamine-induced dopamine release in accumbens

Mattsson A, Schilstrum B, Svensson TH, Olson L (2005) Cortical cholinergic deficiency enhances amphetamine-induced dopamine release in accumbens. Neuroscience 2005 Abstracts 557.8. Society for Neuroscience, Washington, DC.

Summary: Disturbances in cholinergic functions have been implicated in schizophrenia. We have recently shown that cholinergic denervation of neocortex produced by local injection of the immunotoxin 192 IgG-saporin into nucleus basalis magnocellularis (nbm) leads to an increased sensitivity to d-amphetamine in adult female rats. The objective of the current study was to investigate if this effect was paralleled by an increased amphetamine-induced release of dopamine in accumbens. The corticopetal cholinergic projections were lesioned by intraparenchymal infusion of 192 IgG-saporin into nbm in adult rats. D-amphetamine-induced dopamine release in nucleus accumbens was measured by in vivo microdialysis two to three weeks after lesioning. We find that amphetamine causes a greater release of dopamine in rats with cortical cholinergic denervation than in sham lesioned controls. The duration of the amphetamine-effect was also significantly longer in the 192 IgG-saporin lesioned group compared to controls. The results suggest that abnormal responsiveness of mesencephalic dopaminergic neurons could be secondary to cortical cholinergic deficiency. This in turn might constitute one possible contributing pathophysiological factor in schizophrenia.

Related Products: 192-IgG-SAP (Cat. #IT-01)

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