Caffeine Induces Dopamine and Glutamate Release in the Shell of the Nucleus Accumbens

Solinas, Marcello; Ferré, Sergi; You, Zhi‐Bing; Karcz-Kubicha, Marzena; Popoli, Patrizia; Goldberg, Steven R.

doi:10.1523/jneurosci.22-15-06321.2002

Cited by 305 publications

(234 citation statements)

References 22 publications

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“…This hypothesis might seem at odds with the results of several reports that indicate that caffeine can reinstate or prevent the extinction of cocaine-seeking behaviour (Worley et al, 1994;Schenk et al, 1996;Self et al, 1996;Kuzmin et al, 1999;Green and Schenk, 2002;Weerts and Griffiths, 2003). However, these effects of caffeine appear to be due to A 1 rather than A 2A receptor blockade (Kuzmin et al, 1999;Green and Schenk, 2002, Solinas et al, 2002, 2005Karcz-Kubicha et al, 2003;Quarta et al, 2004Quarta et al, 2005Antoniou et al, 2005). Thus, caffeine and selective A 1 receptor antagonists have many behavioral, subjective and biochemical similarities to other psychostimulants, including their ability to induce dopamine release in the nucleus accumbens (Solinas et al, 2002(Solinas et al, , 2005Karcz-Kubicha et al, 2003;Quarta et al, 2004aQuarta et al, , 2004bAntoniou et al, 2005).…”

Section: Adenosine a 2a Receptors In The Ventral Striatum And Drug-sementioning

confidence: 95%

“…However, these effects of caffeine appear to be due to A 1 rather than A 2A receptor blockade (Kuzmin et al, 1999;Green and Schenk, 2002, Solinas et al, 2002, 2005Karcz-Kubicha et al, 2003;Quarta et al, 2004Quarta et al, 2005Antoniou et al, 2005). Thus, caffeine and selective A 1 receptor antagonists have many behavioral, subjective and biochemical similarities to other psychostimulants, including their ability to induce dopamine release in the nucleus accumbens (Solinas et al, 2002(Solinas et al, , 2005Karcz-Kubicha et al, 2003;Quarta et al, 2004aQuarta et al, , 2004bAntoniou et al, 2005). Nevertheless, we should distinguish between acute and chronic caffeine treatment.…”

Section: Adenosine a 2a Receptors In The Ventral Striatum And Drug-sementioning

confidence: 99%

“…Nevertheless, we should distinguish between acute and chronic caffeine treatment. We recently demonstrated that A 1 receptor antagonism plays a key role in the acute motor-activating, discriminative stimulus and dopamine-releasing effects of systemically administered caffeine in rats (Solinas et al, 2002(Solinas et al, , 2005Karcz-Kubicha et al, 2003;Quarta et al, 2004aQuarta et al, , 2004bAntoniou et al, 2005). However, the A 1 receptor antagonistic effects disappear with chronic treatment with caffeine, while A 2A receptor antagonistic effects remain (Karcz-Kubicha et al, 2003;Quarta et al, 2004a).…”

Section: Adenosine a 2a Receptors In The Ventral Striatum And Drug-sementioning

confidence: 99%

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Adenosine A2A receptors in ventral striatum, hypothalamus and nociceptive circuitry

Ferré

Diamond

Goldberg

et al. 2007

Progress in Neurobiology

128

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Adenosine A 2A receptors localized in the dorsal striatum are considered as a new target for the development of antiparkinsonian drugs. Co-administration of A 2A receptor antagonists has shown a significant improvement of the effects of L-DOPA. The present review emphasizes the possible application of A 2A receptor antagonists in pathological conditions other than parkinsonism, including drug addiction, sleep disorders and pain. In addition to the dorsal striatum, the ventral striatum (nucleus accumbens) contains a high density of A 2A receptors, which presynaptically and postsynaptically regulate glutamatergic transmission in the cortical glutamatergic projections to the nucleus accumbens. It is currently believed that molecular adaptations of the cortico-accumbens glutamatergic synapses are involved in compulsive drug seeking and relapse. Here we review recent experimental evidence suggesting that A 2A antagonists could become new therapeutic agents for drug addiction. Morphological and functional studies have identified lower levels of A 2A receptors in brain areas other than the striatum, such as the ventrolateral preoptic area of the hypothalamus, where adenosine plays an important role in sleep regulation. Although initially believed to be mostly dependent on A 1 receptors, here we review recent studies that demonstrate that the somnogenic effects of adenosine are largely mediated by hypothalamic A 2A receptors. A 2A receptor antagonists could therefore be considered as a possible treatment for narcolepsy and other sleep-related disorders. Finally, nociception is another adenosine-regulated neural function previously thought to mostly involve A 1 receptors. Although there is some conflicting literature on the effects of agonists and antagonists, which may partly be due to the lack of selectivity of available drugs, the studies in A 2A receptor knockout mice suggest that A 2A receptor antagonists might have some therapeutic potential in pain states, in particular where high intensity stimuli are prevalent.

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Section: Adenosine a 2a Receptors In The Ventral Striatum And Drug-sementioning

confidence: 95%

Section: Adenosine a 2a Receptors In The Ventral Striatum And Drug-sementioning

confidence: 99%

Section: Adenosine a 2a Receptors In The Ventral Striatum And Drug-sementioning

confidence: 99%

See 1 more Smart Citation

Adenosine A2A receptors in ventral striatum, hypothalamus and nociceptive circuitry

Ferré

Diamond

Goldberg

et al. 2007

Progress in Neurobiology

128

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show abstract

“…On the other hand, microdialysis studies showed that dopamine levels rise in the brains of rats after an acute caffeine administration, suggesting a direct effect of the ergogenic compound on dopamine synthesis. This effect was also dependent on the dose of caffeine used, and therefore on the elicited levels of caffeine in the brain tissue [31]. However, these data were contradicted by a report performed on humans, demonstrating that caffeine increases striatal dopamine D2/ D3 receptor availability and not dopamine levels at doses that are relevant to human consumption [25].…”

mentioning

confidence: 90%

Potential pitfalls when investigating the ergogenic effects of caffeine in mice

Solano¹,

Scheffer²,

Alves³

et al. 2017

J Syst Integr Neurosci

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Caffeine (1,3,7-trimethylxantine) is the most commonly consumed social drug in western society for increased physical and cognitive performance [1][2][3][4][5], and it is the main ergogenic resource used by athletes [6]. Initially controversial, caffeine was banned by the International Olympic Committee from 1980-2003 [1,6,7], but then in 2004 its use was approved by the World Anti-doping Agency (WADA), and later this year by the U.S. Anti-doping Agency (USADA; 2016). However, caffeine has remained on the lists of monitored substances of these anti-doping agencies. Caffeine is rapidly and completely absorbed by the gastrointestinal tract and is readily distributed throughout all tissues of the body, including muscles and the central nervous system (CNS), which are believed to be the main recipients of caffeine's ergogenic effects [2,14]. Ergogenic doses of caffeine ranging from 3 to 9 mg/kg body mass [6] appear to have no adverse effects. A moderate oral dose of 6 mg/ kg body mass, which elicits peak plasma levels of about 60 µmol/L concentrations after 30 to 60 min, with half-life for elimination range between 2.5-10 h, is known to enhance physical and cognitive performance [5,6,10,14,15]. Blood levels of 1 -2 mmol/L are known to be toxic and even lethal [14], and have been associated with suicides [16]. Caffeine's molecular mechanisms for increasing physical performance are still virtually undefined. However, due to its ability to cross the blood-brain barrier at blood concentrations generated by a moderate ergogenic dose, and because of its properties as a stimulant psychotropic drug [15,17], mechanisms involving metabolic and central effects have been proposed.Metabolic effects of caffeine have been mainly related to the enhancement of lipolysis, fatty acid oxidation and energy expenditure via the stimulation of the sympathetic nervous system [18,19] and a sequential sparing of muscle glycogen [20]. However, the main pharmacological effects of caffeine appear to be mediated via the CNS where caffeine counterbalances the inhibitory neuromodulation of adenosine in order to induce effects on both the CNS and peripheral nervous system to reduce pain and exertion perception [21], to improve motor recruitment [22] and to increase excitation-contraction coupling [23,24].Caffeine is a non-selective competitive adenosine receptor antagonist (A 1 R and A 2 AR subtypes) that increases neurotransmission via dopamine D 2 receptors (D 2 R) [25,26]. The striatum expresses high levels of A 2 AR where they are co-expressed with postsynaptic D 2 R, forming A 2 AR-D 2 R heterodimers [25]. In this scenario, caffeine fails to be ergogenic in the mouse lacking A 2 AR [27], or in wild type rats treated with the selective A 2 AR agonist 5'-N-ethylcarboxamidoadenosine (NECA) [26], which denotes the participation of these receptors in caffeine's central-mediated ergogenic effects.When designing experimental models to better define the molecular mechanisms involved in the enhanced capacity of caffeine to positively modulate physical ...

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“…Blockade of adenosine receptors within the striatal regions amplifies dopamine neurotransmission (Fuxe et al, 2007). Caffeine increases extracellular dopamine in the striatum and prefrontal cortex (Borycz et al, 2007;De Luca et al, 2007;Solinas et al, 2002) and dopamine receptor antagonism blocks caffeine-induced locomotor activity (Garrett and Holtzman, 1994;Nehlig et al, 1994). Thus, caffeine's actions in the brain are likely due to both adenosine receptor antagonism as well as amplification of dopamine neurotransmission.…”

Section: Introductionmentioning

confidence: 99%

Effects of Adolescent Caffeine Consumption on Cocaine Sensitivity

O’Neill

Levis

Schreiner

et al. 2014

Neuropsychopharmacol

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Caffeine is the most commonly used psychoactive substance, and consumption by adolescents has risen markedly in recent years. We identified the effects of adolescent caffeine consumption on cocaine sensitivity and determined neurobiological changes within the nucleus accumbens (NAc) that may underlie caffeine-induced hypersensitivity to cocaine. Male Sprague-Dawley rats consumed caffeine (0.3 g/l) or water for 28 days during adolescence (postnatal day 28-55; P28-P55) or adulthood (P67-P94). Testing occurred in the absence of caffeine during adulthood (P62-82 or P101-121). Cocaine-induced and quinpirole (D 2 receptor agonist)-induced locomotion was enhanced in rats that consumed caffeine during adolescence. Adolescent consumption of caffeine also enhanced the development of a conditioned place preference at a sub-threshold dose of cocaine (7.5 mg/kg, i.p.). These behavioral changes were not observed in adults consuming caffeine for an equivalent period of time. Sucrose preferences were not altered in rats that consumed caffeine during adolescence, suggesting there are no differences in natural reward. Caffeine consumption during adolescence reduced basal dopamine levels and augmented dopamine release in the NAc in response to cocaine (5 mg/kg, i.p.). Caffeine consumption during adolescence also increased the expression of the dopamine D 2 receptor, dopamine transporter, and adenosine A 1 receptor and decreased adenosine A 2A receptor expression in the NAc. Consumption of caffeine during adulthood increased adenosine A 1 receptor expression in the NAc, but no other protein expression changes were observed. Together these findings suggest that caffeine consumption during adolescence produced changes in the NAc that are evident in adulthood and may contribute to increases in cocaine-mediated behaviors.

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Caffeine Induces Dopamine and Glutamate Release in the Shell of the Nucleus Accumbens

Cited by 305 publications

References 22 publications

Adenosine A2A receptors in ventral striatum, hypothalamus and nociceptive circuitry

Adenosine A2A receptors in ventral striatum, hypothalamus and nociceptive circuitry

Potential pitfalls when investigating the ergogenic effects of caffeine in mice

Effects of Adolescent Caffeine Consumption on Cocaine Sensitivity

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