Effect of Acute and Chronic Treatment with Risperidone on the Serotonin and Dopamine Receptors in the Rat Brain.
- Author:
Yun Young CHOI
;
Dae Hyuk MIIN
;
Hye Kyung SON
;
Chang Yoon KIM
;
Chul LEE
;
Hee Kyung LEE
- Publication Type:Original Article
- Keywords:
Preamplifier;
Amplifier;
Nuclear Instrument Module;
Energy resolution;
Energy linearity
- MeSH:
Animals;
Antipsychotic Agents;
Autoradiography;
Brain*;
Dopamine*;
Hand;
Humans;
Male;
Nucleus Accumbens;
Peritoneal Cavity;
Rats*;
Rats, Wistar;
Receptors, Dopamine D2;
Receptors, Dopamine*;
Receptors, Serotonin, 5-HT2;
Risperidone*;
Sensory Receptor Cells;
Serotonin*
- From:Korean Journal of Nuclear Medicine
1997;31(1):9-18
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
The therapeutic efficacy of antipsychotic drugs is generally attributed to their ability to block dopamine D2 receptors. Classical D2 antagonists are not effective to treat negative symptoms and produce extrapyramidal side effects. On the other hand, atypical antipsychotic agents ameliorate negative symptoms without producing extra-pyramidal side effects, and it is reported to be associated with blockade of serotonin 5-HT2 receptors. The purpose of this study was to evaluate the effect of risperidone on neuroreceptors in the rat brain by quantitative autoradiography method. In acute treatment group, risperidone was injected into peritoneal cavity of male Wistar rats with dose of 0, 0.1, 0.25, 0.5, 1,0 and 2.0mg/kg in each Group(5/group), and they were decapitated after 2 hours. In chronic treatment group, risperidone was injected with dose of 0, 0.1, and 1mg/kg(I.P.) for 21 days and decapitated after 24 hours following last treatment. The effect of risperodone on the binding of [3H]spiperone to 5-HT2 and D2 receptors were analysed in 4 discrete regions of the striatum, nucleus accumbens, and frontal cortex by quantitative autoradiography. Acute treatment with risperidone reduced cortical 5-HT2 specific [3H]spiperone binding to 32% of vehicle-treated control. Subcortical 5-HT2 specific [3H]spiperone binding was not affected at all dose groups whereas a significant reduction (57%) in D2 specific [3H]spiperone binding was observed in risperidone treated group at doses of l-2mg/kg. Chronic treatment with risperidone produced a decrease in the maximal number of cortical 5-HT2 receptors to 51% and 46% of control in 0.1mg/kg & 1mg/kg treated group respectively. In conclusion, risperidone is a cortical serotonin receptor antagonist with relatively weak antagonistic action on dopamine receptors. These effects on neuroreceptors may explain the therapeutic effect of risperidone as a atypical antipsychotic agents.