Orexins and Animal Behavior
What are orexins?
Orexin-A
and orexin-B (also called hypocretin-1 and hypocretin-2) are two
neuropeptide hormones that are
formed from a common precursor in the hypothalamus. These
hormones are then transported throughout many parts of the brain.
There are two types of orexin receptor
in the brain, one of which preferentially binds orexin-A, while the
other binds both hormones equally well. Many behavioral effects
are attributed to orexin-A but not orexin-B. These hormones are thought to help coordinate an animal's
sleep-wake cycle with its metabolic activity and feeding behavior. Although
other hormones also affect appetite, sleep, and arousal,
orexins seem to play an important role in coordinating these
systems.
The disease narcolepsy is believed to be caused in mice, dogs,
and humans by problems with either producing or recieving orexin.
(Image source)
Although orexins are
found in most vertebrate animals, their functions
have only been studied extensively in mammals. Some known
behavioral effects of orexin are listed below:
Appetite
- Food consumption increases with injection of orexin-A, if given at times when when normal food intake is low.
- Fasting leads to increased levels of orexin.
- Drinking behavior increases with centrally injected orexins.
- Less food is consumed than normal with disfunctional orexin receptors.
- Spontaneous feeding in fasted rats decreases when anti-orexin antibodies are administered.
Reward
- Rats
conditioned to expect a food or drug (but not other type of) reward
have higher levels of orexin than rats that do not anticipate a reward.
- Conditioned rats no longer seek out food and drug rewards when an orexin agonist is administered.
- Reward-seeking behavior can be reinstated in rats by orexin injections.
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Activity
- Mice who lack orexin become obese.
- Increased activity levels are correlated with increased orexin.
- Locomotor activity increases with injections of orexin.
- Activity reduces when orexin system is damaged.
- Narcoleptics- who have disfunctional orexin systems- can
have episodes of cataplexy (spontaneous muscle atrophy during
periods of excitement-- one of the symptoms of narcolepsy).
- Orexin levels increase in active waking over quiet waking, and are correlated with motor activity.
Sleep and Waking
- Narcolepsy, which includes daytime sleepiness,
episodes of REM sleep during periods of wakefulness and waking episodes
during sleep, is caused by inactive orexin pathways.
- Proportion of time spent in REM versus non-REM sleep changes in the absense of orexin.
- Wakefulness is correlated with increased orexin neuron activity.
- Sleep is correlated with reduced orexin neuron activity.
- Circadian rhythms may partially control orexin levels.
- Wakefulness in rodents dose-dependently increases with i.c.v. injections of orexin-A.
- Mice without orexin show less wakefulness in anticipation of feeding than mice with normal amounts of orexin.
(References)
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