Inhibition of Orexin-1/2 Receptors Disrupts Goal-Oriented Locomotor Activity During Motivated Behaviour in Male Rats

Abstract

Orexinergic neurons in the lateral hypothalamic area project to the major wake-promoting areas of the brain and regulate many behavioural states. There are two subtypes of orexin neuropeptides (orexin-1, OX1, and orexin-2, OX2) that act on both orexin receptors 1 and 2 (OX1R and OX2R) in the brain. Some of the goal-oriented behaviour involves intense motor activities where orexin might be playing a role. During male sexual behaviour, the male rats indulge in intense motor activities while chasing the female to make sexual contact. In the present study, we utilized the male sexual behaviour model in rats to study the intense goal-oriented locomotor activity during motivated behaviour. The locomotor activity of sexually active male rats during sexual behaviour was assessed after 4 µl intracerebroventricular injection of either 50 nM of SB-334867 (OX1 receptor antagonist) or suvorexant (OX1 and OX2 receptor antagonist) in the presence of an estrous and a non-estrous female. Male rats treated with SB-334867 and suvorexant showed reduced locomotor activity during sexual behaviour in the presence of an estrous female. SB-334867 further delayed acts of male sexual behaviour by increasing pursuit latency, intromission latency, and mean inter-intromission interval. The overall sexual drive was also decreased in male rats treated with SB-334867. The results of this study suggest that orexin boosts goal-directed locomotor activities during sexually motivated behaviour.