Neurotoxicity induced by caffeine in the thalamocortical system: Role of intracellular calcium-dependent mechanisms and intrinsic properties

PERISINOTTI, PAULA; RIVERO-ECHETO, MARIA CELESTE; KARGIEMAN, LUCILA; CORREA, FLORENCIA; RODRIGUEZ-LEONE, NAZARENA; JUNGE, STEPHANIE; VILLALBA, SOFIA; BERNARDI, MARIA ALEJANDRA; BISAGNO, VERÓNICA; URBANO, FRANCISCO J.

Natural Molecules in Neuroprotection and Neurotoxicity

ElSevier

Lugar: Amsterdam; Año: 2023;

Caffeine is consumed worldwide and frequently used as an active adulterant in many illicit drugs,such as cocaine. This chapter discusses the effects of caffeine and its combination with cocaine on the thalamocortical physiology, focusing on the somatosensory thalamocortical circuit and membraneintrinsic properties. The expression of a wide group of membrane channels that open at the restingmembrane potential level critically defines the characteristics of the firing pattern of thalamocorticalneurons and they are key targets of stimulants. Low-threshold voltage-gated T-type and hyperpolarization-activated cyclic nucleotide-gated (HCN) conductances are dysregulated by eitheracute or chronic binge administrations of caffeine. We finally discuss how systemic administration ofthese stimulants is associated with abnormally high intracellular [Ca2+], which might mediate long-lasting neurotoxic effects on a wide number of the intracellular.