Modulators of consciousness: caffeine and alcohol
It is known that the modulation of synaptic transmission may affect the level of consciousness. Effects produced by caffeine, a common ingredient of tea and coffee are a good example. Using animal anesthesia as a model, Fox et al (2020) reported that caffeine is able to reverse the unconsciousness induced by light anesthesia in adult rats (Foxet al. , 2020). Subsequently, Fong et al (2018) showed that caffeine injected intravenously accelerate human emergence from isoflurane anesthesia (Fong et al. , 2018). These results provide strong evidence that brain excitatory indeed play an important role in the loss of consciousness during anesthesia, and it is possible to explore the basic mechanisms of consciousness using pharmacological approaches in both human and animals. Interestingly, they also found that alteration of anesthesia and consciousness levels are correlated well with brain electroencephalogram (EEG) activity, a common parameter obtained in humans. At the cellular level, it is believed that caffeine produced this effect by increasing intracellular cAMP level, triggering immediate early genes, and regulation of the dopamine- and cAMP-regulated phosphoprotein, M(r) 32 kDa (Lindskog et al. , 2002; Fisone et al. , 2004) and inhibit neuronal adenosine A receptors in the brain.
Alcohol is well known to cause unconsciousness or death when it is consumed at higher dosages. At a low dose range, alcohol can cause disinhibition and anxiolytic effects (Harrison et al. , 2017). Cumulative evidence indicates that alcohol affects both excitatory and inhibitory transmission in the brain (Zorumski et al. , 2014). One of the key actions is that alcohol enhances the actions of γ-aminobutyric acid (GABA) at certain GABAA receptors and inhibits the function of NMDA receptors. Effects of alcohol on AMPA as well as KA receptors have also been reported. It is thus predictable that alcohol also affects central synaptic plasticity such as LTP. These actions provide a basic mechanism of CNS dysfunction caused by alcohol such as memory impairment, blackouts, and loss of consciousness.