Utility of ethological analysis to overcome locomotor confounds in elevated maze models of anxiety

The elevated plus-maze is a commonly used model to identify putative anxiol ytic and anxiogenic drugs. However, the validity of elevated plus-maze and other recently developed variants such as the elevated zero-maze has recent ly been questioned on the grounds that both the reference anxiolytic drug c hlordiazepoxide and the psychostimulant d-amphetamine increase open arm exp loration and stimulate locomotor activity. These findings suggest that meas ures of ''anxiety'' in the elevated maze cannot be adequately dissociated f rom simple changes in locomotor activity, which may confound the interpreta tion of results obtained using these models. A variety of approaches to ass ess drug effects on locomotor activity in the elevated maze have been sugge sted, including the use of total and closed arm entries, as well as supplem entary tests such as exploration of the holeboard apparatus. However, all t hese approaches utilise the measurement of exploration in a novel environme nt, and as such, could potentially be influenced by either changes in anxie ty or locomotor activity. Recently, it has been shown that ethological meas ures of ''risk assessment'', such as stretched-attend postures and head-dip ping, are sensitive indicators of drug-effects in the elevated maze. The pr esent study assessed the utility of ethological analysis in dissociating lo comotor activity from ''anxiety'' by comparing the effects of d-amphetamine to those of chlordiazepoxide in the rat elevated zero-maze. The results sh owed that both chlordiazepoxide and d-amphetamine increase the amount of ti me spent in the open arms and reduce "risk assessment" without increasing l ine crossing or rearing. These results confirm that under certain test cond itions, psychostimulants are capable of producing ''false-positives'' in el evated maze models, and that both traditional methods and the ethological m easures used in this study fail to unequivocally dissociate drug effects on anxiety from effects on locomotor activity. Further studies using other sp ecies and different classes of psychostimulants are warranted to determine the generality of these findings. (C) 1998 Elsevier Science Ltd. All rights reserved.