Effects of depot drug formulations in procedures used to evaluate antipsychotic activity in rodents

The use of long-acting depot antipsychotics results in an increase in compl iance and significantly decreases rates of relapse and rehospitalization of schizophrenic patients. However, the assessment of activity of such drugs in small animals is not as straightforward as the evaluation of acutely act ive drugs. Previous studies have investigated the effects of depot formulat ions by assessing their activity in preclinical methods that examine their striatal dopaminergic components alone. These methods are currently used to examine the extrapyramidal side-effects of antipsychotic agents. In the li ght of recent drug developments, however, it is possible that such procedur es may no longer be appropriate for testing antipsychotics which produce fe wer side effects and which have a broader range of action including nondopa minergic components. Accordingly, the present study aimed to further invest igate the activities of clinically used depot antipsychotics by using proce dures that are considered more predictive of antipsychotic activity rather than extrapyramidal side-effect liability. Along with acutely active analog s, flupenthixol decanoate, fluphenazine decanoate, and haloperidol decanoat e were examined in the following procedures with rats or mice: antagonism o f 1 [2,5-dimethoxy-4-iodophenyl]-2-aminopropane (DOI) -induced behaviors an d amphetaminestimulated locomotion. Effects of the depot formulations in bo th procedures were determined at time points ranging from 24 h to 14 days a fter administration. In general, some antipsychotic-related effects were ob served with the drugs particularly at earlier time points; effects at 14 da ys were minimal. The results from this study demonstrate that depot formula tions of antipsychotic drugs have effects in rodents, but factors possibly related to injection volume, test procedure, and species could limit the du ration of action in small laboratory animals. (C) 1999 Wiley-Liss, Inc.