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 dopamine 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 detection 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 conditions can impact upon other physiological responses to apomorphine such as drug-induced hypothermia. In mice, apomorphine 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 stereotypic behavior were similar in both. By contrast, apomorphine-induced locomotion was more prominent in the novel exploratory 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 discussed with particular emphasis upon conducting psychopharmacological challenge tests in rodents.
Harkin
A
A
Department of Pharmacology, National University of Ireland, Galway, Ireland.
Kelly
J P
JP
Frawley
J
J
O'Donnell
J M
JM
Leonard
B E
BE
D000704:Analysis of Variance; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D001831:Body Temperature / Q000187:drug effects; D003342:Corpus Striatum / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D011597:Psychomotor Performance / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013239:Stereotyped Behavior / Q000187:drug effects
D001058:Apomorphine; D004298:Dopamine