**1. Introduction**

Depression is a prevalent and severe brain disorder that hits many people; it is estimated that it occurs at a 12 months prevalence rate of 7% in Europe [1]. Major depression is mainly characterized by depressed mood, anhedonia, loss of general interest and fatigue. Depression is associated with brain changes in various areas of the prefrontal limbic network [2]. This network involves the orbitofrontal cortex, anterior and posterior cingulate cortex, insula, amygdala, hippocampus and thalamus [3]. Regions associated with olfactory processes have a large overlap with those areas in the prefrontal limbic network and it has been suggested that (reduced) olfaction might be a (cognitive) marker for depression [4]. Croy et al. [5] showed that reduction of olfactory associated functions in the brain of depressed women improved with antidepressant (psycho) therapy to normal control levels, indicating that olfaction may represent a marker for depression. A connection between olfaction and depressive behavior has come strongly forward with the introduction of the olfactory bulbectomized (OBX) rat (see reviews by refs. [6, 7]).

The OBX rat has been strongly advocated as an animal model of depression for various reasons. Rajkumar and Dawe [8] gave an extensive overview and critical discussion on the commonalities between the OBX model and perturbations in the frontal cortex of the human depressed brain. Although it is clear that the brain and behavioral changes in the OBX-brain (of rats) are not directly comparable to the changes in the brain (in particular the frontal cortical areas) of depressed humans, there are considerable similarities that support at least a (partial) role of the OBX rat as modeling (part of) human depressive behaviors [7, 9]. In this paper, the OBX model as used for almost two decades in our laboratory is used. Activity as parameter for detecting 'depression' aspects in rats is widely used and accepted as a sensitive measure of antidepressant effects of various manipulations (antidepressants). Standard use is the measurement of the activity of rats in an Open Field (open arena) during a short test (lasting between 10 and 30 minutes in general). In our research, we also applied telemetric measurements (heart rate, body temperature and activity) in the home cage to measure more refined parameters like day-night rhythms. The present paper is in particular a reflection of our scientific work on the OBX rat model as one of the best (if not the best animal model) model of human depression that can be used to study aspects of the process of depression that cannot be directly studied in humans.
