MODULATION OF PHENCYCLIDINE-INDUCED CHANGES IN LOCOMOTOR-ACTIVITY ANDPATTERNS IN RATS BY SEROTONIN

To test the hypothesis that serotonergic modulation of the effects of phencyclidine (PCP) are due to circuit- rather than receptor-based int eractions between glutamatergic and serotonergic systems, multivariate profiles of rat behavior were assessed after treatments with the 5-hy droxyhyptamine (5-HT) 5-HT2 receptor antagonist ketanserin (1.0 mg/kg) , the 5-HT2 receptor agonist (1(2,5-dimethoxy-4-iodophenyl)-2-aminopro pane) (DOI; 0.27 mg/kg), various doses of PCP (0.75 to 10.125 mg/kg), or combinations thereof. Ketanserin blocked all effects of DOI, but re duced the effects of PCP only on locomotion. Depending on the dose, PC P was observed to increase or decrease locomotion and the roughness of the rats' patterns of locomotion. In any case, DOI always increased t he activity and decreased the roughness of locomotor paths in PCP-trea ted rats. Thus, co-administration of DOI and PCP did not yield a shift in the dose-effect curve for either drug, but instead resulted in a n ew behavioral profile consistent with a circuit-based dynamic interact ion. (C) 1998 Elsevier Science B.V.