Adenosine and Dopamine Receptor Interactions in Striatum and Caffeine-induced Behavioral Activation

Abbreviations: 6-HDA, 6-hydroxydopamine; AjAR, type 1 adenosinergic receptor; A_2AAR, type 2A adenosinergic receptor; AC, adenylyl cyclase; AMPA, a-amino-3-hydroxy-5-methylisoxazole-4-propionic acid; aMPT, a methylparatyrosine; AR, adenosine receptor; CNS, central nervous system; CREB, cAMP response element binding protein; D₁R, type 1 dopaminergic receptor; D₂R, type 2 dopaminergic receptor; DAT, dopamine transporter; DPCPX, 8-cyclopentyl-1,3-dipropylxanthine; ERK, extracellular signal-related kinase; GABA, y-aminobutryic acid; GPe, globus pallidus externa; G protein, guanine nucleotide binding protein; GPi, globus pallidus interna; IEG, immediate early gene; KO, knock-out; l-DOPA, 3,4-dihydroxy-L-phenylalanine; mGluR, metabotropic glutamate receptor; MPTP, 1-methyl 4-phenyl 1,2,3,6-tetrahydropyridine; MSN, medium spiny neurons; NMDA, N-methyl-D-aspartic acid; PD, Parkinson disease; PKA, protein kinase A; SNc, substantia nigra pars compacta; SNr, substantia nigra pars reticulata; TH, tyrosine hydroxylase; VTA, ventral tegmental area 



This review will examine how dopamine, a monoamine neurotransmitter, and adenosine, a neuromodulator, regulate behavioral activation, primarily as reflected by locomotor activity in rodents. Two neuronal circuits in the brain, known as the direct and indirect pathways of the basal ganglia, regulate locomotion by jointly determining the intensity of thalamic stimulation to motor cortex. Dopamine and adenosine bind to guanine nucleotide binding protein (G protein)-coupled receptors present on neurons of these pathways and thereby modulate neurotransmission. Dopamine is synthesized in neurons that originate in substantia nigra pars compacta (SNc) and the ventral tegmental area (VTA) of the brain and is released at synapses in striatum. The 5 subtypes of dopamine receptors (DR) fall into 2 categories in light of their pharmacologic features: 1) the D₁-like receptors (D₁R and D₅R) couple to excitatory G_s/olf protein and 2) the D₂-like receptors (D₂R, D₃R, and D₄R) couple to inhibitory G_i protein. D₁R and D₂R are the 2 major subtypes present in striatal locomotor circuits. When stimulated by an agonist, these receptors generate opposing intracellular signals. D₂R also are located presynaptically on dopamine neurons, where they act as autoreceptors and suppress dopamine synthesis and release. read more A word about Prednisone