Neurochemistry of Wakefulness

Wakefulness

• Wakefulness is regulated by the balance of excitatory and inhibitory neurochemicals.
• Excitatory neurochemicals include glutamate, acetylcholine, dopamine, norepinephrine, orexin, and histamine.
• Inhibitory neurochemicals include GABA, melatonin, and adenosine.

Neural Control of Wakefulness

• Reticular Formation: Releases glutamate in the forebrain.
• Basal Forebrain: Releases acetylcholine in the forebrain.
• Locus Coeruleus: Releases norepinephrine in the forebrain.
• Hypothalamus: Crucial for wakefulness. Damage to the posterior hypothalamus can disrupt wakefulness. Releases histamine and orexin to the forebrain. The loss of orexin-producing neurons causes narcolepsy.
• Suprachiasmatic Nucleus (SCN): The brain's internal clock, controlling melatonin release by the pineal gland.

Caffeine

• Caffeine is an adenosine receptor antagonist.
• Adenosine suppresses excitatory neurochemicals (dopamine, norepinephrine, glutamate, acetylcholine) and enhances GABA activity.
• Adenosine accumulates during the day.
• A cup of coffee contains ~100 mg of caffeine, a can of soda ~40 mg.
• Caffeine is metabolized by CYP-IA2.
• Half-life is ~4 hours, with active metabolites extending effects.
• Caffeine constricts cerebral vessels, aiding in headaches.
• Coffee consumption may protect against type 2 diabetes, cancer, Parkinson's, Alzheimer's, cardiovascular disease, and improve memory, but it can exacerbate anxiety.

Sleep Stages

• Brain activity varies during wakefulness.
• Brain activity becomes increasingly rhythmic from Stages 1 to 4 (slow-wave sleep).
• Sleep isn't the absence of brain activity.
• Stages 3-4 slow wave sleep are characterized by rhythmic brain activity, presumably as the hypothalamus stops sending signals to the cortex.
• REM sleep is linked to body temperature.
• REM deprivation leads to REM rebound.
• Some drugs (e.g., barbiturates, alcohol) suppress REM sleep.
• Higher body temperature correlates with more REM sleep.

Insomnia

• Insomnia is highly comorbid with anxiety.
• Types of insomnia include onset, maintenance, and termination.
• Body temperature falling promotes sleep onset, while rising temperature promotes wakefulness.

Sleep Aids

• Many over-the-counter sleep aids are antihistamines, with the 'Z-drugs' (e.g., Zolpidem, Zaleplon, Eszopiclone) considered for insomnia.
• These are Non-benzodiazepine receptor agonists (NBZRAs) with varying half-lives (1-6 hours).
• These bind to 1-2 GABA receptor subunits, not all 5.
• Some sleep aids can cause amnesic states.
• Ramelteon (Rozerem) is a melatonin agonist with a questionable efficacy.
• Oxerin receptor antagonists (e.g., Suvorexant - Belsomra) target orexin pathways, preventing arousal system activation. Orexin is a peptide neurotransmitter regulating sleep-wake transitions.

This quiz explores the complex neurochemical landscape that regulates wakefulness, focusing on the roles of excitatory and inhibitory substances. It delves into the neural control mechanisms including key brain structures such as the reticular formation and hypothalamus, as well as the impact of caffeine on these processes.