In the field of anxiety research, animal models are used as screening tools in the search for compounds with therapeutic potential and as simulations for research on mechanisms underlying emotional behaviour. However, a solely pharmacological approach to the validation of such tests has resulted in distinct problems with their applicability to systems other than those involving the benzodiazepine/GABA A receptor complex. In this context, recent developments in our understanding of mammalian defensive behaviour have not only prompted the development of new models but also attempts to refine existing ones. The present review focuses on the application of ethological techniques to one of the most widely used animal models of anxiety, the elevated plus-maze paradigm. This fresh approach to an established test has revealed a hitherto unrecognized multidimensionality to plus-maze behaviour and, as it yields comprehensive behavioural profiles, has many advantages over conventional methodology. This assertion is supported by reference to recent work on the effects of diverse manipulations including psychosocial stress, benzodiazepines, GABA receptor ligands, neurosteroids, 5-HT 1A receptor ligands, and panicolytic/panicogenic agents. On the basis of this review, it is suggested that other models of anxiety may well benefit from greater attention to behavioural detail.

No abstract

Recent research on the effects of selective 5-HT1A receptor antagonists in animal models of anxiety has yielded inconsistent findings. In the present study, the behavioural effects of the novel 5-HT1A receptor antagonist, 4-(2'-methoxy-phenyl)-1-[2'-(n-2"-pyridinyl) -p-iodobenzamido]-ethyl-piperazine (p-MPPI), were examined in male mice using an ethological version of the elevated plus-maze test. Results show that at lower doses (0.5-4.5 mg/kg), p-MPPI produced a significant and dose-related anxiolytic profile on both conventional (open arm avoidance) and ethological (risk assessment) measures. However, these effects were lost at a higher dose (13.5 mg/kg) which, instead, increased grooming and immobility. The behavioural profile of p-MPPI is contrasted with those previously obtained with other 5-HT1A receptor ligands (agonists, partial agonists and antagonists), and it is suggested that 5-HT1A receptor antagonists may possess therapeutic advantages in anxiety disorders.

No abstract

No abstract