Effects of the Clozapine on the Suppressed Spontaneous Alternation Behaviour in Rats

Cheon, Kang Hoon; Lee, Gi Chul; Lee, Jung Ho; Choi, Young Min; Jeon, Seong Ill; Jung, Hong Kyung; Ryu, Jeong Whan; Choi, Mee

Abstract

OBJECTIVES
The study was designed to evaluate the role of the 5-HT2 and dopanmine D2 antagonist on spontaneous alternation behaviour which is an animal model of obsessive compulsive disorder in rat. On the basis of serotonin-dopamine interaction hypothesis, the effect of clozapine was evaluated by applying the suppressed spontaneous alternation behaviour model.
METHODS
The apparatus for spontaneous alternation behaviour was a black plexiglas T-maze with distinctive black and white goal boxes. Black guillotine doors separated the start box and the goal boxes from the main body of the T-maze. Small cups of chocolate milk were placed in the corners of both goal boxes. At 24 hours prior to experiment, rats(spraque-Dawley) were food-deprived. The food-deprived rate were put into T-maze, in which both goal during which it was placed in the start box and allowed to choose one of the goal boxes for each time. The mean number of choices until the occurrence of spontaneous altemation behaviour were checked. After baseline of the number of choices of spontaneous altemation behaviour was stabilized, the spontaneous altemation was disrupted by nonselective 5-HT agonist, 5-MeODMT(1.25mg/kg/IP). The experimental animals were stratified nito 5 groups : clomipramine(5mg/kg/IP), clozapine(10mg/kg/IP), clozapine(20mg/kg/IP), haloperidol(0.1mg/kg/IP), and saline(0.2cc/IP) control groups. They all went through 21 days fo treatment(intraperitoneal). The protective effects against the 5-McODMT-induced disruption of spontaneous alternation behaviour were evaluated on the next day of drug treatment in each group.
RESULTS
1) SAB was supressed by 5-McODMT injection. 2) After 21 days of the drug treatment, the clozapine and the clomipramine groups showed significant difference from the haloperidol and the saline control groups in the reversal of 5-McODMT-induced from the haloperidol and the saline control groups in the reversal of 5-MeODMT-induced suppression of spontaneous altermation behaviour. 3) The clozapine(20mg/kg/IP) group was superior to the clomipramine group in the protective effect of 5-MeODMT-induced suppression of spontaneous alternation behaviour.
CONCLUSION
In clinical situation, the we think that atypical antipsychotic drugs those acting as serotonin and dopamine receptor antagonist with no extrapyramidal side effect can be beneficial to improve the symptoms of obsessive-compulsive disorder.