Caffeine, Adenosine Receptors, and Synaptic Plasticity

Abstract

Abstract. Few studies to date have looked at the effects of caffeine on synaptic plasticity, and those that did used very high concentrations of caffeine, whereas the brain concentrations attained by regular coffee consumption in humans should be in the low micromolar range, where caffeine exerts pharmacological actions mainly by antagonizing adenosine receptors. Accordingly, rats drinking caffeine (1 g/L) for 3 weeks, displayed a concentration of caffeine of circa 22 µM in the hippocampus. It is known that selective adenosine A1 receptor antagonists facilitate, whereas selective adenosine A2A receptor antagonists attenuate, long term potentiation (LTP) in the hippocampus. Although caffeine is a non-selective antagonist of adenosine receptors, it attenuates frequency-induced LTP in hippocampal slices in a manner similar to selective adenosine A2A receptor antagonists. These effects of low micromolar concentration of caffeine (30 µM) are maintained in aged animals, which is important when a possible beneficial effect for caffeine in age-related cognitive decline is proposed. Future studies will still be required to confirm and detail the involvement of A1 and A2A receptors in the effects of caffeine on hippocampal synaptic plasticity, using both pharmacological and genetic approaches.

Acute caffeine administration impact on working memory-related brain activation and functional connectivity in the elderly: A BOLD and perfusion MRI study

“…Early studies postulated that caffeine's effects on brain activation depend on a complex and potentially regionally variable interaction of neuronal and vascular responses (Laurienti et al, 2003;Koppelstaetter et al, 2010). At the neuronal level, caffeine causes most of its biological effects via the antagonism of all types of adenosine receptors A1, A2A, A3, and A2B mainly in the striatal neurons projecting to the basal ganglia (for reviews see Fisone et al (2004) and Costenla et al (2010)). Besides this antagonism, it enhances the sensitivity of striatal GABAergic synapses to the stimulation of cannabinoid CB1 receptors and at high concentrations inhibits phosphodiesterases and promotes calcium release from intracellular stores (Rossi et al, 2010).…”

Caffeine Increases Hippocampal Sharp Waves <i>in Vitro</i>

“…Note that the concentration of normally taken caffeine in the human brain under physiological conditions is estimated to reach tens of µM. [19][20][21][22][23] Within 5 min of perfusion with 60 µM caffeine, the incidence of SWs increased to approximately 200%, and the increase was stably maintained in the presence of caffeine (Fig. 1C left).…”

“…However, the major forms of the adenosine receptors in the brain are A 1 and A 2A receptors. 23) Thus, we examined the A 1 receptor-selective antagonist DPCPX (K D =3.9 nM in human) and the A 2A receptor-selective antagonist SCH58261 (K D =0.6 nM in human). 25) Likewise caffeine, 100 nM DPCPX increased the incidence of SWs ( Fig.…”

Nutrition Therapy Regulates Caffeine Metabolism with Relevance to NAFLD and Induction of Type 3 Diabetes

“…Caffeine excess with aging is relevant to magnesium deficiency [97][98][99] and relevant to neuron calcium dyshomeostasis [17,100] that is connected to SCN dysynchrony critical to the maintainance of circadian rhythms [7]. Disturbances in neurons by caffeine involve neuron calcium disturbances that involve the adenosine receptors, synapses and neuron networks [101,102] with detrimental effects on the central nervous system with irreversible T3D [36,37]. Sirt 1 regulation of SCN synchrony and neuron synapse plasticity is completely corrupted by caffeine as caffeine overload in the CNS occurs with aging process.…”