Sleep, Eat, Sex – Orexin Has Something to Say

Orexin is a neuropeptide which is released by the posterior lateral hypothalamus, and is linked to wakefulness and sleep, appetite regulation, and the motivation of sexual and addictive behaviors.  One apt way to think about it is as a hormone in the brain, combining some of the popularly conceived effects of adrenaline and testosterone into one. 

(Don’t get too excited now!  I am just trying to give you a way to think about it, that orexin works to promote arousal and response…)

I am writing a post on the links of orexin to appetitive behavior, particularly addiction, but I’ve generated a lot of material.  So I am going to give you this one first, which summarizes aspects of orexin (also known as hypocretin) and neurological function with respect to sleep, appetite and sex. 

Sleep:

Orexin is definitely involved in arousal and wakefulness, for example, in getting sleepy or drowsy people to be more awake (with little effect on arousal in already rested individuals).  In other words, orexin might be a way to combat fatigue in the future.  There’s a whole Wired article, Snorting a Brain Chemical Could Replace Sleep, on it.  As the Wired article puts it, “it cures sleepiness,” at least in monkeys in some pretty controlled conditions.  Besides treatment of narcolepsy, other possible uses being considered are for pilots on long flights and people suffering from jet lag.

 For the science behind it, there are some links: Promoting Wakefulness: http://www.jneurosci.org/cgi/content/abstract/27/52/14239; Possible Sleep Medication: http://www.nature.com/nm/journal/v13/n2/abs/nm1544.html; Narcolepsy & Low Orexin: http://www.pnas.org/cgi/reprint/0400590101v1.pdf 

Appetite:

Orexin plays a key role in promoting eating and appetite, and seems to work to signal “eat more.”  It’s hypothesized as one main component for getting people to eat beyond satiety (and here I thought Thanksgiving dinners were the reason).  

 For example, Rodgers et al. (2002) argue, “These data suggest that orexin-1 receptors mediate the episodic signalling of satiety and appear to bridge the transition from eating to resting in the rats’ feeding-sleep cycle. The argument is developed that the diverse physiological and behavioural effects of orexins can best be understood in terms of an integrated set of reactions which function to rectify nutritional status without compromising personal survival.”

 Or, in this report “Obesity: Is It In Your Head?,” the reporter notes, “Some brains may be wired to encourage fidgeting and other restless behaviors that consume calories and help control weight, according to new research published by The American Physiological Society.  The study found that the brains of rats bred to be lean are more sensitive to a chemical produced in the brain, orexin A, which stimulates appetite and spontaneous physical activity such as fidgeting and other unconscious movements. Compared to rats bred to be obese, the lean rats had a far greater expression of orexin receptors in the hypothalamus.  ‘The greater expression of orexin receptors suggests the lean rats’ brains were more sensitive to the orexin the brain produces,’ said Catherine M. Kotz, the study’s senior researcher.”

 Other research shows orexin plays a role in increased sensitivity to sensory cues.  Julliard et al. (2007) write, “Orexin therefore increases and leptin decreases olfactory sensitivity. Orexin and leptin modulate the olfactory performance in a similar way as do physiological induced fasting and satiation and appear to be important factors in the interdependency of olfaction and food intake.”  In other words, orexin on its own makes rats as sensitive to olfactory cues as being hungry. 

To sum up, orexin plays a role in driving eating beyond satiety and in sedentary behavioral inclinations, as well as in sensory sensitivity.  In turn, these connect to exercise, environmental cues, emotions, and cognition.  Put differently, our culture can drive our biology, particularly in the domain of appetite, into realms of excess.  That is the basic conclusion, in my mind, of the following article “Eating for Pleasure or Calories.”  The abstract reads:
 

A changing environment and lifestyle on the background of evolutionary engraved or perinatally imprinted physiological response patterns is the foremost explanation for the current obesity epidemic. However, it is not clear what the mechanisms are by which the modern environment overrides the physiological controls of appetite and homeostatic body weight regulation. Major advances have been made regarding crosstalk between metabolic signals and the cognitive/emotional brain that primarily deals with the environment. On one hand, metabolic signals such as leptin and ghrelin have previously unexpected direct effects on learning and memory, as well as liking and wanting. On the other hand, brain areas involved in reward, cognition, and executive control can override metabolic regulation by talking to the hypothalamus. 

Sex:

As one article puts it, “Besides playing a role in the regulation of feeding and energy homeostasis in rats, ORs appear to increase sexual arousal as well as copulatory performance in rats.”

 So here’s one relevant piece by Guliaa et al. (2003): “The medial preoptic area plays an important role in the regulation of male sexual behavior in rats, and this area receives orexinergic inputs… The results of the study showed that orexin A application at the medial preoptic area increased sexual arousal as well as the copulatory performance. Sexual arousal is one of the physiological stimuli, which influences wakefulness.”  (I can see the pharmaceutical companies now—rather a cigarette, have a little nasal orexin and another go-round.)

And a more recent article by Muschamp et al. (2007), which concludes “Together, these data support the view that hcrt/orx peptides may act in a steroid-sensitive manner to facilitate the energized pursuit of natural rewards like sex via activation of the mesolimbic DA system.”