Effects of Newer Antipsychotic Drugs on Apomorphine-Induced Climbing Behavior in Mice

Jeong, Seong Hoon; Kim, Jin Young; Kim, Eyong; Chung, In Won

Abstract

OBJECTIVE
Chlorpromazine equivalence was used to chart relative potencies of typical antipsychotic agents and it has been known to be in a linear relationship with dopamine D2 receptor affinity. After the introduction of these newer antipsychotic drugs, the role of other neurotransmitter systems than dopamine has been emphasized, and it is difficult to attribute the diverse effect of these drugs to common mechanism. Recently, several equivalent dose guidelines have been published for newer antipsychotic drugs. In this study, antagonism of apomorphine-induced climbing behavior was used to investigate the relationship between the clinically determined equivalent doses and behavioral effects measured by animal model of several newer antipsychotic drugs. METHOD: Several newer anti-psychotic drugs were administered 20 min before apomorphine injection. After apomorphine injection, climbing behavior was assessed for up to 20 min by visual inspection. The doses that had inhibited 50% of the control group behavior was defined to be Half-Effective Doses (HED) and calculated from the regression line. The relationship between the HED and clinical Minimum Effective Doses (MED) published elsewhere was investigated using linear regression analysis. RESULT: All the antipsychotic drugs antagonized the apomorphine-induced climbing behavior in a dose-dependent manner. Statistically significant correlation between HED and MED was found (Spearman's rho=0.96, p<0.001), and statistically significant linear relationship was also found (F=76.2, df=1, 4, p=0.001; r2=0.950). CONCLUSION: Antipsychotics inhibit apomorphine-induced climbing behavior by D2 antagonism. Therefore, the result suggests that the common mechanism underlying the therapeutic effects of newer antipsychotics might be related with dopamine D2 antagonism. However, the equivalent doses used in this study focused mainly on psychotic and behavioral symptoms, so that they are not qualified to embrace multi-dimensional therapeutic effects of newer antipsychotics. Investigation of the relationship between the equivalent doses focused on each symptom domain and the effects on diverse neurotransmitter system would broaden our knowledge of mechanism of action of newer antipsychotics.