Behavioral and neurochemical profile of m-CPP following exposure to single restraint stress in rat

The present study was designed to monitor the responsiveness of 5-hydroxytryptamine (5-HT; serotonin)-2C receptors following the exposure to restraint stress in rats. Rats were restrained for 2 hours. 24-h after the termination of the restraint period, 1-(m-Chlorophenyl)piperazine (m-CPP; a 5-HT-2C agonist) at the doses of 1.5 mg/kg or 3.0 mg/kg and saline (1 ml/kg), was injected to unrestrained and restrained animals. Hypolocomotive effects (home cage activity, open field activity and motor coordination) and anxiogenic-like effects (light-dark activity and plus maze activity) were successively monitored in each animal after the drug or saline administration. Rats were decapitated 1-h post-injection to collect brain samples for neurochemical estimation by HPLC-EC. Our results show that differences in the hypolocomotive and anxiogenic-like effects of m-CPP between restrained and unrestrained animals could not be demonstrated in the present experimental paradigm. This was due to the fact that the behavioral effects were already marked after restraint leaving little room for an additional m-CPP effect. The effects of m-CPP on increasing 5-hydroxyindole acetic acid (5-HIAA) and decreasing dihydroxy phenyl acetic acid (DOPAC) levels were more pronounced (p < 0.01) in restrained than unrestrained animals. The results suggest that behavioral responses to m-CPP and stress are similar The attenuation of m-CPP changes in 5-HIAA and DOPAC levels may be due to a decreased responsiveness of 5-HT-2C receptors in restrained animals.