Test conditions influence the response to a drug challenge in rodents

These studies were conducted to examine the differential response to a drug challenge under varied experimental test conditions routinely employed to study drug-induced behavioral and neurophysiological responses in rodents. Apomorphine, a nonselective dopa mine agonist, was selected due to its biph asic behavioral effects, its ability to induce hypothermia, and to produce distinct changes to dopamine turnover in the rodent brain. From such experi ments there is evidence that characterization and detection of apomorphine- induced activity in rodents critically depends upon the test conditions emp loyed. In rats, detection of apomorphine-induced hyperactivity was facilita ted by a period of acclimatization to the test conditions. Moreover, test c onditions can impact upon other physiological responses to apomorphine such as drug-induced hypothermia. In mice, apomorphine produced qualitatively d ifferent responses under novel conditions when compared to those behaviors elicited in the home test cage. Drug-induced gross activity counts were inc reased in the novel exploratory box only, while measures of stereotypic beh avior were similar in both. By contrast, apomorphine-induced locomotion was more prominent in the novel exploratory box. Dopamine turnover ratios (DOP AC:DA and HVA:DA) were found to be lower in those animals exposed to the ex ploratory box when compared to their home cage counterparts. However, apomo rphine-induced reductions in striatal dopamine turnover were detected in bo th navel and home cage environments. The implications of these findings are discussed with particular emphasis upon conducting psychopharmacological c hallenge tests in rodents. (C) 2000 Elsevier Science Inc.