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1. Chronic ingestion of caffeine by male NIH strain mice alters the density of a variety of central receptors. 2. The density of cortical A1 adenosine receptors is increased by 20%, while the density of striatal A2A adenosine receptors is unaltered. 3. The densities of cortical beta 1 and cerebellar beta 2 adrenergic receptors are reduced by ca. 25%, while the densities of cortical alpha 1 and alpha 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. 4. The density of cortical nitrendipine-binding sites associated with calcium channels is increased by 18%. 5. 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.

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