Arousal, the ascending reticular activating system and sedating antihistamines
The ascending reticular activating system (ARAS), going up from the brainstem reticular formation (a set of grey matter nuclei) to the cerebral cortex, maintains arousal, the state of being awake.
Remember
The ARAS keeps the cerebral cortex awake, so its main function is to maintain arousal; a first-generation antihistamine (the older type) causes drowsiness by blocking histamine signalling in this arousal system.
The reticular formation is a set of grey matter nuclei (clusters of nerve cell bodies) scattered through the brainstem. The main job of the reticular formation is to keep the cortex awake, by maintaining arousal and consciousness. Arousal is being awake, and it supports goal-seeking behaviour, for example looking for food or the fight or flight response. Consciousness is awareness of the internal and external environments, and it needs the reticular formation and the cortex to work normally and to stay properly connected.
The pathway connecting the two is the ascending reticular activating system (ARAS). Ascending means going up to the cortex, and activating means waking it up. The reticular formation receives inputs from the sensory systems and from the cortex itself. The cortex also signals back, which helps to hold the brain in a steady awake state.
The ARAS uses cholinergic and histaminergic fibres, meaning nerve fibres that release acetylcholine or histamine, to maintain the awake state. That explains why first-generation antihistamines and anticholinergics (drugs that block acetylcholine) can be sedating. A first-generation antihistamine, the older type, enters the brain and blocks histamine signalling there, so cortical activation falls and the person becomes sleepy even after a good night's sleep. Second-generation antihistamines do not cross the blood-brain barrier (the tightly sealed lining of the brain's blood vessels) readily, and they are clearly less sedating.
Massive damage to the ARAS, or to its connection with the cortex, can cause a variety of disorders of consciousness.
Key facts
- ARAS
- the pathway connecting the reticular formation to the cerebral cortex; its main function is to maintain arousal.
- Reticular formation
- a set of grey matter nuclei spread throughout the brainstem.
- Arousal
- the state of being awake.
- Fibres of the awake state
- cholinergic and histaminergic fibres help to maintain it.
- First-generation antihistamines
- they cross into the brain and have well-known central nervous system effects, including drowsiness.
- Second-generation antihistamines
- they cross the blood-brain barrier poorly and are less sedating.
Exam traps
- Sending outputs to the hypothalamus does not make the reticular formation the main regulator of hormone secretion, because hormone release is regulated mainly by the hypothalamus acting on the pituitary gland.
- Coordinating fine movements is a task for the cerebellum, not the arousal pathway: cerebellar damage impairs fine movements, while damage to the arousal pathway impairs wakefulness.
- Sedation from a first-generation antihistamine does not come from direct depression of cortical neurones alone: the drug reduces histamine signalling in the brain's arousal system, where histamine-using neurones act on the cortex.
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