Within‐session behavioral decrement of atypical antipsychotics: Role of novelty

Abstract

In order to gain a better understanding of the characteristics of antipsychotic-induced within-session decrements in unconditioned behavioral responses of mice, and whether they are sensitive to novel environmental stimuli, we studied the acute effects of haloperidol and atypical antipsychotic drugs (sulpiride, thioridazine, clozapine, and remoxipride) in familiar and novel open-field conditions in mice. The results show that familiarized controls and antipsychotic-treated groups had a progressive reduction in ambulation and rearing during the 10-minute open-field session. By manipulating the configuration of the open-field situation, familiarized controls as well as mice treated with typical or atypical antipsychotic drugs were able to exhibit an enhanced response to the presentation of novel stimuli. It may be noted that both the maintenance and the initiation of ambulation were affected by antipsychotic treatment. Furthermore, when comparing novel versus familiar groups during the 10-minute session, the increase in ambulation induced by atypical antipsychotic treatment was maintained longer (6–8 minutes) than that induced by haloperidol (4 minutes). In summary, these findings show that an important feature in the reinstatement of both typical and atypical antipsychotic-induced behavioral decrement may be a change in the stimulus conditions. Drug Dev. Res. 42:71–75, 1997. © 1997 Wiley-Liss, Inc.