EVIDENCE THAT TOLERANCE TO THE ANXIOGENIC-LIKE EFFECTS OF MCPP DOES NOT INVOLVE ALTERATION IN THE FUNCTION OF 5-HT2C RECEPTORS IN THE RAT CHOROID-PLEXUS

The mechanisms by which 1-(3-chlorophenyl) piperazine (mCPP) causes anxiety are unclear, but it has been suggested that the serotonin 5-HT2C receptor subtype may be involved in this effect. We have therefore studied the effect of chronic treatment (3 weeks) with mCPP in two animal models of anxiety (light/dark choice task in mice and elevated plus-maze test in rats) and subsequently assessed the function of 5-HT2C receptors (measured by maximal stimulation of 5-HT2C receptor-mediated phosphoinositide hydrolysis) in rat choroid plexus, where the receptor is present at very high levels, mCPP treatment regimens led to a tolerance to the anxiogenic-like action of the drug, but failed to alter the second messenger coupling of the 5-HT2C receptors in the choroid plexus, thereby suggesting the involvement of different mechanisms in this behavioral effect.