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Locating the neuronal targets for caffeine
Author(s) -
Fredholm Bertil B.,
Arslan Giulia,
Kull Björn,
Svenningsson Per
Publication year - 1998
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/(sici)1098-2299(199811/12)45:3/4<324::aid-ddr31>3.0.co;2-1
Subject(s) - adenosine a2a receptor , caffeine , neuroscience , adenosine , dopaminergic , dopamine , adenosine receptor , stimulation , adenosine receptor antagonist , dopamine receptor d2 , dopamine receptor , receptor , biology , chemistry , pharmacology , endocrinology , agonist , biochemistry
Caffeine is the most widely consumed of all psychoactive drugs. In doses that induce behavioral stimulation it acts primarily on adenosine A 2A and possibly A 1 receptors. Actions on the latter appear to be very much involved with regulation of the stimulatory glutamatergic input to several neuronal structures, including the striatum. Adenosine A 2A receptors are found enriched on a subpopulation of GABAergic output neurons from the striatum, where they coexist with dopamine D 2 receptors. The two receptors interact, both at the membrane level and by having opposing effects at the level of second messengers. Inhibition of adenosine A 2A receptors by the selective antagonist SCH 58261 causes motor stimulation and a decrease in the expression of immediate early genes in these striatopallidal neurons. This effect is also clearly seen when dopamine D 2 activation is blocked, either by preventing dopaminergic impulse flow or by receptor blockade. Thus, a tonic effect of endogenous adenosine is specifically antagonized by adenosine receptor antagonists such as caffeine. Despite a strictly delimited primary effect, secondary interactions between neurons lead to changes in the activity of several groups of neurons in interconnected networks. These changes likely underlie the behavioral effects of caffeine. Drug Dev. Res. 45:324–328, 1998. © 1998 Wiley‐Liss, Inc.