Affective disorders are often accompanied by changes in anxiety and motivation to engage in active behaviours. We have developed an exploration-based behavioural test which allows distinguishing between rats belonging to clusters with persistently high anxiety/low motivation to explore the environment and low anxiety/high motivation to explore (LE- and HE-rats, respectively). The LE-rats are consistently more anxious and use passive coping strategies in several tests of affective disorders, and have concordant deviations in the monoaminergic neurochemistry and brain oxidative metabolism. Genome-wide microarray analysis of gene expression in three brain regions known to be involved in mood disorders (raphe, hippocampus, and the frontal cortex) revealed signifi cant alterations in the expression of several neurotransmission-related genes expected to be relevant to affect (e.g. downregulation of Gabra1, Gabra4, Gabrg1, Gabrg2, Glrb, Htr1a, Htr2c, Tph2, and upregulation of Gria3, Grin2a, and Cnr1) in the LE- vs. HE-animals. Also, overrepresentation of differentially expressed genes involved in the Wnt signalling pathway in all three brain regions, and the MAPK signalling, long-term potentiation and long-term depression pathways in the hippocampus and the frontal cortex suggests that the behavioural differences between rats with persistently high or low exploratory activity may be related to differences in synaptic plasticity in the raphe nuclei as well as its projection areas.
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