Effects of 5-hydroxytryptamine, receptor antagonism on the behavioral activation and immediate early gene expression induced by dizocilpine

The noncompetitive N-methyl-D-aspartate (NMDA) antagonists dizocilpine and phencyclidine cause behavioral changes in animals that can be blocked by an tipsychotic agents, implicating NMDA receptors in the expression of schizop hrenic symptoms. In the present study, we examined the effects of dizocilpi ne (0.1-3.0 mg/kg s.c,) on locomotor activity and on the expression of c-fo s and hsp-70 immediate-early genes (IEGs) in mice. Results indicate that di zocilpine increases locomotor activity and selectively increases the expres sion of c-fos and hsp-70 in the posterior cingulate cortex. Haloperidol (0. 01-0.1 mg/kg) and clozapine (0.6-1.25 mg/kg) block both the locomotor respo nse and the increased IEG immunoreactivity induced by dizocilpine (0.6 mg/k g). The 5-HT2 antagonists ritanserin (0.06-0.25 mg/kg), ketanserin (0.03-0. 12 mg/kg) and amesergide (0.3-1.25 mg/kg) also significantly attenuated the locomotor response to dizocilpine. Haloperidol and clozapine suppressed th e head weaving induced by dizocilpine, but ritanserin, as previously report ed did not. Although some attenuation of the c-fos and hsp-70 immunoreactiv ity was seen with the 5-HT2 antagonists it was less pronounced than that in duced by haloperidol or clozapine. In conclusion, 5-HT2 antagonists as well as antipsychotic compounds attenuate the locomotor response to dizocilpine in mice. Haloperidol and clozapine appear to be more effective, however, i n attenuating the expression of c-fos and hsp-70 in the posterior cingulate gyms than 5-HT2 antagonists ritanserin, ketanserin or amesergide. We thus have seen a dissociation in the capacity of compounds to alter the effects on behavior and IEG expression after dizocilpine administration.