NEUROPSYCHOPHARMACOLOGY OF THE NUCLEUS INCERTUS: STUDY OF ITS FUNCTION IN LOCOMOTION, DEPRESSION AND ANXIETY

Abstract

The nucleus incertus (NI) is an evolutionarily conserved brainstem structure whose functional relevance is poorly understood. Based on the widespread anatomical connections, variety of neuromodulators and receptors, and strong theta modulation, the hypothesis was that the NI is able to modulate arousal and behavioural activity levels. D2 receptor mRNA and protein was found to be expressed in the rat NI and appears to promote hypolocomotion. Electrical microstimulation of the NI in behaving rats robustly evoked locomotion. A loss-of-function study showed that the NI promotes passive coping, behavioural inhibition and anxiety-induced arousal. 5-HT1A receptors in the NI play a role in the anxiogenic response of a high dose of buspirone suggesting that they may be involved in promoting anxiety physiologically. In conclusion, the NI appears to modulate behavioural activity levels, stress-coping, arousal and anxiety differentially based on its activation level and presence of stressors via the availability of varied neuromodulators.