Caffeine Regulates Neuronal Expression of the Dopamine 2 Receptor Gene

Stonehouse, Anthony H.; Adachi, Megumi; Walcott, Elisabeth C.; Jones, Frederick S.

doi:10.1124/mol.64.6.1463

Cited by 25 publications

(21 citation statements)

References 37 publications

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“…In mammals, CAFF induces the expression of D2 receptors in vivo and in vitro (9); however, it is unknown if the D1 receptor is under similar transcriptional regulation. To determine if changes in expression of dDA1 are correlated with wake-inducing properties of CAFF in Drosophila, we analyzed the expression of dDA1 mRNA in the heads of WT f lies following STE and LTE to CAFF.…”

Section: Adenosinergic and Dopaminergic Systems Mediate Wake-promotingmentioning

confidence: 99%

“…Dopaminergic action on both the D1 and D2 receptors contributes to the alert waking state, based on the action of centrally administered D1 and D2 agonists in rodents (8). Molecularly, CAFF modulates D2 transcription in vitro and in vivo (9). Motor-activating effects of CAFF are diminished in D2R mutant mice (10,11); however, the role of D2R in the arousing effect of CAFF remains unknown, and functional tests of the brain regions mediating these effects are lacking in mammals.…”

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confidence: 99%

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Drosophila D1 dopamine receptor mediates caffeine-induced arousal

Andretic

Kim

Jones

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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The arousing and motor-activating effects of psychostimulants are mediated by multiple systems. In Drosophila, dopaminergic transmission is involved in mediating the arousing effects of methamphetamine, although the neuronal mechanisms of caffeine (CAFF)-induced wakefulness remain unexplored. Here, we show that in Drosophila, as in mammals, the wake-promoting effect of CAFF involves both the adenosinergic and dopaminergic systems. By measuring behavioral responses in mutant and transgenic flies exposed to different drug-feeding regimens, we show that CAFFinduced wakefulness requires the Drosophila D1 dopamine receptor (dDA1) in the mushroom bodies. In WT flies, CAFF exposure leads to downregulation of dDA1 expression, whereas the transgenic overexpression of dDA1 leads to CAFF resistance. The wakepromoting effects of methamphetamine require a functional dopamine transporter as well as the dDA1, and they engage brain areas in addition to the mushroom bodies.ptimal behavioral performance in humans and animals depends on an adequate arousal level, which often involves diffuse afferent inputs from the dopaminergic system. Caffeine (CAFF) displays strong arousing properties and is the most consumed psychoactive drug in the world. CAFF competitively inhibits adenosine A1 and A2 receptors, antagonizing the effects of the sleep-promoting neuromodulator adenosine that accumulates during waking (1). CAFF also leads to increased dopaminergic and glutamatergic transmission in different striatal subcompartments, which has been linked to its activating and reinforcing effects (2-4).Although CAFF-induced wakefulness has been related to modulation of cholinergic and histaminergic arousal systems (5, 6), CAFF's induction of increased dopaminergic transmission and its effect on wakefulness have not been adequately examined. Animals with increased dopaminergic transmission, such as dopamine transporter (DAT) mutant mice, have decreased non-rapid eye movement sleep and increased sensitivity to the wake-promoting action of CAFF (7). Dopaminergic action on both the D1 and D2 receptors contributes to the alert waking state, based on the action of centrally administered D1 and D2 agonists in rodents (8). Molecularly, CAFF modulates D2 transcription in vitro and in vivo (9). Motor-activating effects of CAFF are diminished in D2R mutant mice (10, 11); however, the role of D2R in the arousing effect of CAFF remains unknown, and functional tests of the brain regions mediating these effects are lacking in mammals.We have shown previously that the wake-promoting effects of methamphetamine (METH) in Drosophila are mediated through dopaminergic transmission, indicating some evolutionary conservation in the behavioral and neurochemical effects of psychostimulants (12).Treatment of flies with CAFF induces wakefulness; however, the mechanism underlying this activity is currently unknown (13,14). In the present study, we investigate the role of dopamine signaling in the wake-inducing properties of CAFF and METH, with emphasis on the role of the Dr...

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Section: Adenosinergic and Dopaminergic Systems Mediate Wake-promotingmentioning

confidence: 99%

mentioning

confidence: 99%

Drosophila D1 dopamine receptor mediates caffeine-induced arousal

Andretic

Kim

Jones

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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“…These primers gave a 94-base pair PCR product, which was confirmed as a true Cox7c amplification product by automated DNA sequencing. In addition, PCR reactions were performed using ␤-actin gene-specific primers (Adachi et al, 2005) or GAPDH gene-specific primers (Stonehouse et al, 2003) to normalize the expression levels of Cox7c mRNA. PCR products were labeled by incorporating fluorescent dNTPs using the SYBR green PCR master mix (Applied Biosystems, Chatsworth, CA).…”

Section: Methodsmentioning

confidence: 99%

“…For transfection, 6 ϫ 10 5 PC-12 cells were seeded in each well of a six-well plate (Costar; Corning Life Sciences, Acton, MA). Twenty-four hours later, cells were transfected with 1ug of either pGL3 basic, Ϫ2063/ϩ74 construct, or Ϫ93/ϩ74 construct as described previously (Stonehouse et al, 2003). In all experiments, cells were cotransfected with 100 ng of the plasmid pCMV-␤ (Clontech) to assess transfection efficiency and to normalize luciferase activity values to an internal standard of ␤-galactosidase activity.…”

Section: Preparation Of Mouse Cox7c Reporter Constructs and Luciferasmentioning

confidence: 99%

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Caffeine Stimulates Cytochrome Oxidase Expression and Activity in the Striatum in a Sexually Dimorphic Manner

et al. 2008

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Epidemiological studies indicate that caffeine consumption reduces the risk of Parkinson's disease (PD) in men, and antagonists of the adenosine 2A receptor ameliorate the motor symptoms of PD. These findings motivated us to identify proteins whose expression is regulated by caffeine in a sexually dimorphic manner. Using mass spectroscopy, we found that Cox7c, a nuclear-encoded subunit of the mitochondrial enzyme cytochrome oxidase, is up-regulated in the striatum of male but not female mice after receiving a single dose of caffeine. The expression of two other Cox subunits, Cox1 and Cox4, was also stimulated by caffeine in a male-specific fashion. This up-regulation of Cox subunits by caffeine was accompanied by an increase in Cox enzyme activity in the male striatum. Caffeine-induced stimulation of Cox expression and activity were reproduced using the adenosine 2A receptor (A2AR)-specific antagonist 5-amino-7-(2-phenylethyl)-2-(2-furyl)-pyrazolo[4,3-]-

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Combined Effects of Simultaneous Exposure to Caffeine and Cocaine in the Mouse Striatum

et al. 2016

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Caffeine is the world’s most popular psychoactive drug and is also an active adulterant found in many drugs of abuse, including seized cocaine samples. Despite several studies which examine the effects of caffeine or cocaine administered as single agents, little data are available for these agents when given in combination. The purpose of the present study was to determine if combined intake of both psychostimulants can lead to maladaptive changes in striatal function. Mice were injected with a binge regimen (intermittent treatment for 13 days) of caffeine (3 × 5 mg/kg), cocaine (3 × 10 mg/kg), or combined administration. We found that chronic caffeine potentiated locomotion induced by cocaine and that both caffeine-treated groups showed sensitization. Striatal tissue was obtained 24 h and 7 days after last injection (withdrawal) for immunohistochemistry and mRNA expression. Our results show that combined intake of both psychostimulants can increase GFAP immunoreactivity in the striatum at both times post treatment. Gene expression analysis, targeted at dopamine, adenosine, and glutamate receptor subunit genes, revealed significant transcript down-regulation in the dorsal striatum of AMPA, NMDA, D1 and D2 receptor subunit mRNA expression in the group that received combined treatment, but not after individual administration. At withdrawal, we found increased D1 receptor mRNA expression along with increased A1, AMPA, NMDA, and metabotropic subunit expression. A2A mRNA showed decreased expression after both times in all experimental groups. Our study provides evidence that there are striatal alterations mediated by combined caffeine and cocaine administration, and highlights negative outcomes of chronic intake of both psychostimulants.

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Caffeine Regulates Neuronal Expression of the Dopamine 2 Receptor Gene

Cited by 25 publications

References 37 publications

Drosophila D1 dopamine receptor mediates caffeine-induced arousal

Drosophila D1 dopamine receptor mediates caffeine-induced arousal

Caffeine Stimulates Cytochrome Oxidase Expression and Activity in the Striatum in a Sexually Dimorphic Manner

Combined Effects of Simultaneous Exposure to Caffeine and Cocaine in the Mouse Striatum

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