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Adenosine receptor A2a Adenosine receptor A2a Gamma- aminobutyric acid receptor subunit alpha-1 Gamma- aminobutyric acid receptor subunit beta-2 Gamma- aminobutyric acid receptor subunit gamma-2 Alpha-1A adrenergic receptor Histamine H1 receptor Gamma- aminobutyric acid receptor subunit alpha-1 Gamma- aminobutyric acid receptor subunit beta-2 Gamma- aminobutyric acid receptor subunit gamma-2 Orexin Orexin receptor type 2 Gamma- aminobutyric acid receptor subunit beta-2 Gamma- aminobutyric acid receptor subunit gamma-2 Gamma- aminobutyric acid receptor subunit alpha-1 Gamma- aminobutyric acid receptor subunit beta-2 Gamma- aminobutyric acid receptor subunit gamma-2 Vesicular inhibitory amino acid transporter Voltage- dependent calcium channel subunit alpha-2/delta-1 Voltage- dependent L-type calcium channel subunit beta-1 Voltage- dependent L-type calcium channel subunit alpha-1C Glutamate decarboxylase 1 Gamma- aminobutyric acid receptor subunit alpha-1 Caffeine Caffeine Adenosine γ-Aminobutyric acid Norepinephrine Histamine Ca+ γ-Aminobutyric acid γ-Aminobutyric acid γ-Aminobutyric acid Ca+ L-Glutamic acid CO2 Pyridoxal 5'-phosphate Sleep Arousal Arousal Arousal Depolarization Hyperpolarization Locus Coeruleus Lateral Hypothalamus Nucleus accumbens Dendrite Axon Terminal Cytosol Cytosol Postsynaptic Neuron Cytosol Ventrolateral Preoptic Nucleus Tuberomammillary Nucleus Cytosol Postsynaptic Neuron Cytosol Postsynaptic Neuron Caffeine antagnoizes the adenosine A2A receptors in the nucleus accumbens which prevents depolarization of the neuron. GABA cannot be released from the neuron due to the antagonism of adenosine A2A receptors which prevents depolarization of the neuron. The arousal promoting areas of the brain (Locus coeruleus, lateral hypothalamus, and the tuberomammillary nucleus) inhibits the ventrolateral preoptic nuclues in a flip-flop arrangement via GABA The low concentration of GABA cannot activate the GABAA receptors which 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 Orexin receptors activate arousal which leads to wakefulness and alertness. GABA receptors cause hyperpolarization of the neurons which further inhibits the activation of sleep mechanisms. Caffeine increases norepinephrine concentration in the locus coeruleus through an unknown mechanism. Norepinephrine activates alpha and beta adrenergic receptors The activation of adrenergic receptors and the removal of the restraints via GABAA receptors leads to an increase in arousal which promotes wakefulness and alertness. Histamine H1 receptors activate arousal mechanisms in the brain which promote wakefulness. It stimulates many other areas of the brain to further the effects of wakefulness and alertness. Orexin is released through innervation by glutamate via the dorsomedial hypothalamus. Caffeine inhibits adenosine A2A receptors which regularly promote sleep. This further inhibits sleep mechanisms in the brain. Increased arousal in the locus coeruleus, lateral hypothalamus, and the tubermammillary nucleus inhibits the sleep mechanisms of the ventrolateral preoptic nucleus
ADORA2A ADORA2A GABRA1 GABRB2 GABRG2 ADRA1A HRH1 GABRA1 GABRB2 GABRG2 HCRT HCRTR2 GABRB2 GABRG2 GABRA1 GABRB2 GABRG2 SLC32A1 CACNA2D1 CACNB1 CACNA1C GAD1 GABRA1 Caffeine Caffeine Adenosine γ-Aminobutyric acid Norepinephrine Histamine Calcium γ-Aminobutyric acid γ-Aminobutyric acid γ-Aminobutyric acid Calcium L-Glutamic acid Carbon dioxide Sleep Arousal Arousal Arousal Depolarization Hyperpolarization