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Computational biology of sensitization: Pharmacologically- relevant amplification mechanisms
Sensitization is a discussed as an important phenomenon underlying the initiation and progression of a variety of neuropsychiatric disorders as divers as epilepsia, substance-related disorders or recurrent affective disorders. The relevance to understand sensitization phenomena is emphasized by the recent finding that even single exposures to amphetamine can induce longlasting locomotor and HPA-axis sensitization in rats (Vanderschuren et al. J Neurosci 1999;19:9579–86). To address specific questions associated with the temporal dynamics of sensitization development, we recently began computational modelling of neuronal sensitization mechanisms (Huber et al. J Psychiatr Res 2001;35:49–57 and Neuropsychopharmacology 2003;28:S13-S20). In the present study we examine how previously subthreshold external stimuli can – under pathophysiologically altered conditions – become effective trigger leading to self-amplifying activity in a model. Specifically we address the interaction between altered random neuronal activity, as e.g. demonstrated for ethanol in human brains, and temporal stimulus-sensitization coupling. The findings indicate that stochastic resonance effects contribute to stimulus-induced sensitization.