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Pathway Description
Caffeine Nervous Action Pathway
Homo sapiens
Drug Action Pathway
Created: 2022-04-14
Last Updated: 2023-10-25
Caffeine is a central nervous system stimulant present in tea, coffee, cola beverages, analgesic drugs, and agents used to increase alertness. Consistent intake of caffeine increases the population of adenosine receptors, which can potentially lead to a change in potency.
Caffeine stimulates wakefullness and arousal in the central nervous system. Caffeine does this by inhibiting adenosine A2A receptors on the nucleus accumbens. The activation of A2A receptors in the nucleus accumbens releases GABA into the locus coeruleus, the tuberomammillary nucleus, and the lateral hypothalamus in order to regulate these systems through GABA receptors. The inhibition of GABA release leads to the disinhibition of these areas of the brain. The low concentration of GABA cannot activate the GABAA receptors which would cause hyperpolarization of the neurons. The inhibition of GABA removes the restraints on the neurons of the tuberomammillary nucleus, the lateral hypothalmus, and the locus coeruleus.
In the locus coeruleus caffeine activates the release of norepinephrine through an unknown mechanism. Norepinephrine accumulates in the synapse and activates Alpha-1 adrenergic receptors and beta-1 adrenrgic receptors. The inhibition of GABA also leads to the disinhibition of adrenergic neurons in the locus coeruleus, furthers increasing the activation of adrenergic receptors. This activates arousal systems which leads to wakefulness and alertness through different mechanisms throughout the brain.
In the tuberomammillary nucleus, which is in the anterior hypothalamus, histamine activates the H1 histamine receptors. This increases arousal, which leads to increased wakefulness and alertness.The wakefulness center of the brain is suspected to be in the anterior hypothalamus as well. From here it sends projections throughout the brain to promote wakefulness.
In the lateral hypothalamus caffeine inhibits adenosine A1A receptors which leads to the disinhibition of orexin. The inihition of GABA release also causes a disinhibition of orexin. Orexin is released through innervation by glutamate via the dorsomedial hypothalamus. Orexin release activates arousal which leads to the activation of wakefulness and alertness mechanisms throughout the brain.
The lateral hypothalamus, the tuberomammillary nucleus, and the locus coeruleus inhibit the ventrolateral preoptic nucleus via GABA in a flip-flop arangment depending on the area of the brain that is stimulated more.Therefore arousal and wakefulness inhibits sleep, and sleep inhibits arousal and wakefullness. Caffeine also inhibits adenosine A2A receptors present in the ventrolateral preoptic nucleus which further prevents sleep.
References
Caffeine Nervous Pathway References
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