Adenosinergic mechanisms in the brain: Potential targets for the treatment of mood disorders?

Adenosine (ADO) is a neuromodulator with sleep-promoting, anticonvulsive and neuroprotective actions. ADO is released in high amounts when O₂- demand exceeds O₂-supply, such as in anoxia, seizures or sleep deprivation. Increased ADO content in the brain is often accompanied by upregulation of adenosine A₁-receptors, which reinforces ADO’s actions and is mediated by an ADO-induced increased formation and release of interleukin-6 from astrocytes. A₁-receptors mediate inhibition of cholinergic neurons in the tegmentum and basal forebrain, which are active during REM sleep and wakefulness. Their inhibition by ADO thus explains the slow-wave-sleep promoting effects of ADO. Since activation of cholinergic neurons and stimulation with cholinergic agonists is also associated with depressive symptoms, inhibition by ADO of cholinergic neurons might also be important in the mechanism of the antidepressant action of sleep deprivation and ECT, since both are associated with an increase in ADO and upregulation of A₁-receptors. Thus modulation of adenosinergic mechanisms by pharmacological means might eventually prove as a new antidepressant strategy.