Role of the Central Ascending Neurotransmitter Systems in the Psychostimulant Effects of Caffeine

Abstract

Abstract. Caffeine is the most consumed psychoactive drug in the world. It is a non-selective adenosine receptor antagonist that in the brain targets mainly adenosine A1 and A2A receptors. The same as classical psychostimulants, caffeine produces motor-activating, reinforcing and arousing effects. This depends on the ability of caffeine to counteract multiple effects of adenosine in the central ascending neurotransmitter systems. Motor and reinforcing effects depend on the ability of caffeine to release pre-and postsynaptic brakes that adenosine imposes on the ascending dopaminergic system. By targeting A1-A2A receptor heteromers in striatal glutamatergic terminals and A1 receptors in striatal dopaminergic terminals (presynaptic brake), caffeine induces glutamate-dependent and glutamate-independent release of dopamine. These presynaptic effects of caffeine are potentiated by the release of the postsynaptic brake imposed by antagonistic interactions in the striatal A2A-D2 and A1-D1 receptor heteromers. Arousing effects of caffeine depend on the blockade of multiple inhibitory mechanisms that adenosine, as an endogenous sleep-promoting substance, exerts on the multiply interconnected ascending arousal systems. Those mechanisms include a direct A1-receptor mediated modulation of the corticopetal basal forebrain system and an indirect A2A-receptor mediated modulation of the hypothalamic histaminergic and orexinergic systems.

Expectation of having consumed caffeine can improve performance and mood

“…In addition to its arousing effects, evidence indicates that caffeine interacts with neural systems involved in motivation and reward by antagonising the effect of adenosine on the mesocorticolimbic dopamine system (Ferré, 2010;Salamone et al, 2009; although see Nehlig, Armspach & Namer, 2010). The effect of caffeine on reward motivation in humans has received very little attention, but the Card Arranging Reward Responsivity Objective Test (CARROT; Al-Adawi & Powell, 1997) has recently been used to explore this.…”

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

“…It also favors the postsynaptic effect of dopamine by attenuating the antagonistic interactions in the striatal A2A-D2 and A1-D1 receptor heteromers. Arousing properties of caffeine depend on the blockade of multiple inhibitory mechanisms that adenosine, as an endogenous sleep-promoting substance, exerts on the ascending histaminergic and orexinergic systems (Ferre, 2010). Apart from its direct effect on brain cells, caffeine has a marked regulatory effect on brain perfusion.…”

Amethystic agents influencing toxicodynamics of ethanol

“…Низкая активность, либо её отсутствие у некоторых ксантинов объясняется наличием в спектре их фармакологической активности не только способности блокировать аденозиновые рецепторы [77][78][79]. Изобутилметилксантин, кофеин и теофиллин, к примеру, тормозят обратный захват аденозина (т.е.…”

“…оказывают сходное с этанолом действие) [77], а изобутилметилксантин, кроме того, обладает свойствами частичного агониста аденозиновых рецепторов [78]. Не следует забывать о возможности торможения активности фосфодиэстеразы циклических нуклеотидов ксантинами, а также об их способности модулировать другие нейромедиаторные системы [79].…”