A novel pharmacological concept in an animal model of psychosis

Objective: We have analysed pharmacologically induced perturbation of funct ional and structural neurogenesis in the prefrontal cortex (PFC) and hippoc ampus. Method: Juvenile gerbils received a single dose of methamphetamine (METH, 5 0 mg/kg, i.p.). In adults the following parameters were quantitatively inve stigated: prefrontal dopaminergic and GABAergic innervation densities (immu nocytochemistry), morphogenesis of pyramidal cells (Golgi), dentate granule cell proliferation (BrdU-labelling), working memory and behavioural inhibi tion (delayed response, open,field). Results: single challenge of METH continuously suppresses granule cell prol iferation in adult gerbils and initiates rewiring of neuronal networks in t he PFC which run concurrently with the development of severe deficits in PF C-related behaviours. Conclusion: It appears that a continuous remodelling of neuronal circuits i s an inherent property of the brain, the biological significance of which s eems to be to ascertain adaptive interaction between brain and environment. Learning more about drug-induced neuronal reorganization might be basic fo r understanding the genesis of psychotic conditions in the brain. This pres entation is based both on own research and on a review of the literature.