Abbreviations / part 2

Figure 1. Locomotor-regulatory circuits in rodent brain.

Adenosine is produced both intra- and extracellularly from many types of cells and neurons. Four adenosine receptor (AR) subtypes are expressed in brain (A₁, A_2A, A_2B, and A₃). However, only A₁AR and A_2AAR are physiologically important in striatal regulation of behavior, largely because of their relative abundance and affinity for binding agonists. Presynaptically, A₁AR and A_2AAR colocalize on glutamatergic nerve terminals, where they jointly modulate glutamate release. Postsynaptically, dimers of A₁AR with D₁R are present on neurons of direct pathways, whereas A_2AAR with D₂R are on neurons of indirect pathways.
These dimers act through opposing intracellular signaling to modulate neuronal output and, eventually, the amount of locomotor activity. see Cephalexin antibioticThe methylxanthine caffeine is a stimulant drug that acts mostly via nonselective binding to AR (in brain, mainly A₁AR and A_2AAR) at both pre- and post-synaptic sites. By blocking the effects of endogenous adenosine at these receptors, caffeine promotes vigilance, arousal, and attention, which in rodents is reflected by a significant increase in locomotion. At low doses, caffeine blocks presynaptic A₁AR and thereby promotes dopamine and glutamate release from striatal terminals, whereas at high doses, caffeine blocks A_2AAR on glutamate terminals and thereby suppresses such release. Similarly, caffeine's behavioral effects are dose-dependent, with low doses causing behavioral activation and high doses causing suppression. Furthermore, the psychomotor stimulant effect of caffeine after acute dosing depends on blockade of both AjR and A_2AAR, but the effect relies predominantly on A_2AAR blockade after chronic administration. By influencing dopaminergic neurotransmission in striatum, caffeine can ameliorate symptoms of Parkinson disease (PD) in humans and experimental animals.