Inhibition of Orexin-1/2 Receptors Disrupts Goal-Oriented Locomotor Activity During Motivated Behaviour in Male Rats
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ORIGINAL ARTICLE
Inhibition of Orexin‑1/2 Receptors Disrupts Goal‑Oriented Locomotor Activity During Motivated Behaviour in Male Rats Aditi Banerjee1,2 · Trina Sengupta1,3 · Hruda Nanda Mallick1 Received: 8 May 2020 / Revised: 27 July 2020 / Accepted: 14 August 2020 © Springer Nature Singapore Pte Ltd. 2020
Abstract Purpose 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. Methods 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. Results 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. Conclusion The results of this study suggest that orexin boosts goal-directed locomotor activities during sexually motivated behaviour. Keywords Orexin · SB-334867 · Suvorexant · Motivated behaviour · Consummatory locomotor activity
1 Introduction Motivated behaviour is usually evoked by significant emotional cues. The drive for sexual contact is an evolutionarily conserved model of motivated behaviour that demands * Hruda Nanda Mallick [email protected] Aditi Banerjee [email protected] Trina Sengupta [email protected] 1
Neurophysiology Laboratory, Department of Physiology, All India Institute of Medical Sciences, New Delhi 110029, India
2
Department of Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, MA, USA
3
Department of Physiology, All India Institute of Medical Science, Jodhpur, Rajasthan, India
intense coordinated locomotor activity. Active wakefulness is a prerequisite for such motivated behaviour [1, 2]. The hypothalamic neuropeptide, orexin, is associated with wakefulness and vigilance because of its connection to the wakepromoting areas in the brain [3]. Two subtypes of the orexin neuropeptide, orexin-A and orexin-B, are found in lateral hypothalamic neurons and they both bind to orexin type 1 (OX1R) and orexin type 2 (OX2R) receptors [4, 5]. These neuropeptides regulate im
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