Hypothetical dopamine dynamics in mania and psychosis--its pharmacokinetic implications

Abstract

The symptoms of psychosis and mania are both related to dopaminergic hyperactivity. In psychosis, it is proposed that post-synaptic receptor sensitization causes dysfunctional salience processing, leading to the development of delusional symptoms. In various animal models of psychosis, the mechanism of post-synaptic sensitization is related to the increased proportion of high-affinity D2 receptors. On the other hand, psychostimulant-induced increase in synaptic dopamine can serve as a model for manic distractibility. In this study, brief models were constructed to identify the differences in dopaminergic hyperactivity between psychosis and mania, and the effects of antipsychotics were sought in terms of the dynamics of dopamine receptor occupancy. According to the study, it was found that antipsychotics with small Koff value had advantages in restoring the receptor occupancy to normal level in the psychosis model, while in the mania model, those with large Koff value showed a better profile.