Pharmacology Biochemistry and Behavior, Vol. 65, No. 3, pp. 389–398, 2000 © 2000 Elsevier Science Inc. Printed in the USA. All rights reserved 0091-3057/00/$–see front matter PII S0091-3057(99)00210-5 389 Test Conditions Influence the Response to a Drug Challenge in Rodents ANDREW HARKIN, JOHN P. KELLY, JOHN FRAWLEY, JAMES M. O’DONNELL, AND BRIAN E. LEONARD Department of Pharmacology, National University of Ireland, Galway, Ireland Received 7 April 1999; Revised 1 September 1999; Accepted 3 September 1999 HARKIN, A., J. P. KELLY, J. FRAWLEY, J. M. O’DONNELL AND B. E. LEONARD. Test conditions influence the response to a drug challenge in rodents. PHARMACOL BIOCHEM BEHAV 65(3) 389–398, 2000.—These studies were conducted to examine the differential response to a drug challenge under varied experimental test conditions routinely em- ployed to study drug-induced behavioral and neurophysiological responses in rodents. Apomorphine, a nonselective dopa- mine agonist, was selected due to its biphasic behavioral effects, its ability to induce hypothermia, and to produce distinct changes to dopamine turnover in the rodent brain. From such experiments there is evidence that characterization and detec- tion of apomorphine-induced activity in rodents critically depends upon the test conditions employed. In rats, detection of apomorphine-induced hyperactivity was facilitated by a period of acclimatization to the test conditions. Moreover, test condi- tions can impact upon other physiological responses to apomorphine such as drug-induced hypothermia. In mice, apomor- phine produced qualitatively different responses under novel conditions when compared to those behaviors elicited in the home test cage. Drug-induced gross activity counts were increased in the novel exploratory box only, while measures of ste- reotypic behavior were similar in both. By contrast, apomorphine-induced locomotion was more prominent in the novel ex- ploratory box. Dopamine turnover ratios (DOPAC:DA and HVA:DA) were found to be lower in those animals exposed to the exploratory box when compared to their home cage counterparts. However, apomorphine-induced reductions in striatal dopamine turnover were detected in both novel and home cage environments. The implications of these findings are dis- cussed with particular emphasis upon conducting psychopharmacological challenge tests in rodents. © 2000 Elsevier Sci- ence Inc. Environment Rats Mice Apomorphine Challenge Locomotor activity Stereotypy Hypothermia Striatum Dopamine turnover MEASURING spontaneous behaviors is widely applicable to the study of drug action in laboratory animals. The present series of experiments were aimed at a characterization of drug-induced behavioral activity and how the behavioral re- sponse to a given drug differs, depending on the experimental design and test environment. In the present study, a combination of classification by ob- servation and automatic recording was adopted as an appro- priate way to study stereotyped and locomotor behaviors produced by the dopamine agonist, apomorphine (12). Apo- morphine is used extensively as a reference drug in preclinical pharmacology (14); evoking a complex locomotor and stereo- typic response [at low doses (0.1 mg/kg) it reduces locomo- tor activity (6), while at higher doses (0.3 mg/kg) it produces hypermotility and stereotypies (29), reducing body tempera- ture (4) and producing distinct neurochemical responses in rodent brain (23). With apomorphine, we were thus able to study a broad spectrum of drug-induced changes under varied experimental conditions. Drug effects were monitored in two species—the mouse and the rat—and in contrasting auto- mated monitoring systems—an automated home-cage activity monitor, and an automated novel exploratory box. Direct comparisons could then be made between the spontaneous behavior of animals in both tests, alone and in response to the psychostimulant, apomorphine. Such studies are of impor- tance and relevance to studies of general activity, exploration or investigatory behavior, where a major difficulty has been to distinguish between activity related to an animals’ level of arousal, activity elicited by external environmental stimuli, and drug-induced activity (10). Test conditions may not only influence behavior of the ani- mals but can also have an effect on physiological parameters Requests for reprints should be addressed to Andrew Harkin, Ph.D., Department of Pharmacology, National University of Ireland, Galway, Ireland.