Study on the pharmacological basis for the effect of psychological stress in the early life stage on response to psychotropic drugs

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This study aims to elucidate the mechanism for the influence of psychological stress in the early life stage on pharmacological response to psychotropic drugs as a sequel of the enduring changes in development of the neuronal network involving emotion.Fist, we examined the pharmacological basis for the ability of atypical antipsychotic drugs to induce dopamine release in rat prefrontal cortex, using in vivo microdialysis. The results suggest that, depending on the manner of binding to presynaptic dopamine-D2 autoreceptors, different types of atypical antipsychotic drugs may have distinct effects on the activity of dopamine neurons projecting from the ventral tegmental area to the prefrontal cortex. Moreover, the results from the experiment of local application with atypical antipsychotic drugs into the medial prefrontal cortex suggest that the interaction between weak D2 antagonism and potent serotonin (5-HT) 1A receptor agonism within the local circuitry of the prefrontal cortex may c … More ontribute to the ability of clozapine and aripiprazole to increase prefrontal dopamine release. Therefore, expression and maturation of these monoamine receptor subtypes in the prefrontal cortex during the developmental stage may be involved in the clinical response to psychotropic drugs.Second, psychological stress in the early life stage has been thought to increase expression of corticotrophin-releasing factor (CRF), resulting in the enduring effect on development of the neuronal network. We therefore investigated the effect of the selective antagonist for CRF1 receptors on dopamine release in the prefrontal cortex of adult and young rats. As the results, a significant difference in the ability of CRF1 antagonist to modulate stress-induced dopamine release was found between adult (age of six to eight weeks) and young (age of three weeks) rats. These results suggest that the physiological role of CRF1 receptors in the dopaminergic response to stressors may change during the developmental stage. Further studies are needed because individual responses to stressors differed widely. Less