Caffeine and the Brain: An Overview - Caffeine: Chemistry, Analysis, Function and Effects - page 250

different neurotransmitters, such as DA, ACh, noradrenaline and serotonin,
involved in motor activation and reward, in arousal and attention and in the
sleep-wake cycle control. As previously reported, caffeine, at the plasma
concentrations reached with dietary intake, acts mainly through the blockade
of adenosine A 1 and A 2A receptors. A large number of studies have been
performed to investigate the effects of caffeine as such, and with respect to the
involvement of either A 1 and A 2A receptor subtypes, on the release of
neurotransmitters. The majority of these studies have been performed by in
vivo brain microdialysis which permits to analyze changes of concentrations of
neurotransmitters in the synaptic cleft before and after the administration of
drugs. Over the years, this approach has permitted to study, in vivo, the release
of neurotransmitters in a wide range of animal models of neuropsychiatric
disorders such as depression, schizophrenia and drug addiction. Here, we
shortly review the literature on the effects of caffeine administration on in vivo
DA, ACh, noradrenaline and serotonin neurotransmission in different brain
regions as determined by microdialysis.
The understanding of the interactions between caffeine and DA transmis-
sion appears critical to characterize how caffeine may affect motor activation,
psychomotor stimulation and motivated behaviors. In this regard, micro-
dialysis studies, referring to three DA-rich brain areas, i.e. the striatum, the
AcbSh and AcbC and the PFCx, have revealed that these interactions are quite
complex as a consequence of adenosine and DA receptors co-localization and
as a consequence of the opposite control on signal transduction mechanisms
exerted by adenosine and DA. Thus, caffeine was reported to increase
extracellular DA transmission (Okada et al 1996) but it was also reported to
decrease it in the presence of an A 1 receptor antagonist (Okada et al 1996;
1997) suggesting that, under these conditions, caffeine requires both A 1 and
A 2A receptors in order to activate DA transmission. Unfortunately, to our
knowledge the effects of systemic administration of caffeine on in vivo DA
transmission in the striatum have not been described and, since in the above
studies caffeine was administered locally through the microdialysis probe, this
evidence cannot be functional to characterize its effects after systemic
administration. Contrasting results have also been reported by studies
addressing the effects of systemic caffeine administration on DA transmission
in the AcbSh and AcbC. The relevance of these results highly depends on the
significance attributed to DA transmission in these forebrain DA-rich
structures. In fact, preferential increases of DA transmission in the shell of
the Acb, compared to the core, represent a neurochemical index of addictive
properties of drugs (Di Chiara 2002), while drug-induced increases of DA
transmission in the PFCx have been suggested to represent an index of the
psychomotor stimulant properties but not of the addictive properties of drugs
(Di Chiara 2002). Thus, while some authors reported failure to detect increases
of DA in both shell and core compartments of the Acb (Acquas et al 2002; De
Luca et al 2007), others reported the opposite (Solinas et al 2002; Borycz et al
2007).

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