A novel pharmacological concept in an animal model of psychosis.
OBJECTIVE
We have analysed pharmacologically induced perturbation of functional and structural neurogenesis in the prefrontal cortex (PFC) and hippocampus.


METHODS
Juvenile gerbils received a single dose of methamphetamine (METH, 50 mg/kg, i.p.). In adults the following parameters were quantitatively investigated: prefrontal dopaminergic and GABAergic innervation densities (immunocytochemistry), morphogenesis of pyramidal cells (Golgi), dentate granule cell proliferation (BrdU-labelling), working memory and behavioural inhibition (delayed response, open-field).


RESULTS
A single challenge of METH continuously suppresses granule cell proliferation in adult gerbils and initiates rewiring of neuronal networks in the PFC which run concurrently with the development of severe deficits in PFC-related behaviours.


CONCLUSIONS
It appears that a continuous remodelling of neuronal circuits is an inherent property of the brain, the biological significance of which seems to be to ascertain adaptive interaction between brain and environment. Learning more about drug-induced neuronal reorganization might be basic for understanding the genesis of psychotic conditions in the brain. This presentation is based both on own research and on a review of the literature.
Dawirs
R R
RR
University of Bielefeld, Faculty of Biology, Department of Neuroanatomy, Germany.
Teuchert-Noodt
G
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D018759:Adrenergic Uptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D000818:Animals; D018891:Dentate Gyrus / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D005849:Gerbillinae; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007150:Immunohistochemistry; D007266:Inhibition, Psychological; D008694:Methamphetamine / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D009415:Nerve Net / Q000187:drug effects / Q000378:metabolism; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D011618:Psychotic Disorders / Q000175:diagnosis / Q000188:drug therapy*; D011930:Reaction Time / Q000187:drug effects
D018759:Adrenergic Uptake Inhibitors; D008694:Methamphetamine; D004298:Dopamine