Chronic caffeine alters the density of adenosine, adrenergic, cholinergic, GABA, and serotonin receptors and calcium channels in mouse brain

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Abstract
Chronic ingestion of caffeine by male NIH strain mice alters the density of a variety of central receptors. The density of cortical A1 adenosine receptors is increased by 20%, while the density of striatal A2A adenosine receptors is unaltered. The densities of corticalβ 1 and cerebellarβ 2 adrenergic receptors are reduced byca. 25%, while the densities of corticalα 1 andα 2 adrenergic receptors are not significantly altered. Densities of striatal D1 and D2 dopaminergic receptors are unaltered. The densities of cortical 5 HT1 and 5 HT2 serotonergic receptors are increased by 26–30%. Densities of cortical muscarinic and nicotinic receptors are increased by 40–50%. The density of cortical benzodiazepine-binding sites associated with GABAA receptors is increased by 65%, and the affinity appears slightly decreased. The density of cortical MK-801 sites associated with NMDA-glutaminergic receptors appear unaltered. The density of cortical nitrendipine-binding sites associated with calcium channels is increased by 18%. The results indicate that chronic ingestion of caffeine equivalent to about 100 mg/kg/day in mice causes a wide range of biochemical alterations in the central nervous system.