Involvement of adenosine in the neurobiology of schizophrenia and its therapeutic implications

Lara, Diogo R.; Dall'Igna, Oscar Phelippe Permigotti; Ghisolfi, Eduardo S.; Brunstein, Miriam Garcia

doi:10.1016/j.pnpbp.2006.02.002

Cited by 129 publications

(110 citation statements)

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“…1 The adenosine A1 and A2A receptor antagonists theophylline and caffeine decrease P50 sensory gating in normal volunteers, mimicking the findings in schizophrenic patients, 15 and caffeine exacerbates symptoms of schizophrenia. 3 Moreover, the psychostimulant effects of caffeine are blocked by D2 receptor antagonists.…”

Section: Discussionmentioning

confidence: 65%

“…1 The neuromodulator adenosine acts on A1, A2a, A2b and A3 receptors. Activation of adenosine A1R inhibits the release of several neurotransmitters, such as glutamate, dopamine, serotonin and acetylcholine, and decreases neuronal activity by post-synaptic hyperpolarization.…”

Section: Introductionmentioning

confidence: 99%

“…5 For these reasons, it has been suggested that low adenosine activity is involved in schizophrenia. 1 Adenosine deaminase (ADA) participates in purine metabolism by converting either adenosine or 2'-deoxyadenosine into inosine or 2'-deoxyinosine, respectively. Further metabolization of these deaminated nucleosides leads to hypoxantine, which can be either transformed into uric acid by xanthine oxidase or salvaged into mononucleotides by hypoxanthine-guanine phosphoribosyltransferase.…”

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confidence: 99%

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Lower frequency of the low activity adenosine deaminase allelic variant (ADA1*2) in schizophrenic patients

Dutra

Ottoni

Lara

et al. 2010

Rev. Bras. Psiquiatr.

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Objective: Adenosine may play a role in the pathophysiology of schizophrenia, since it modulates the release of several neurotransmitters such as glutamate, dopamine, serotonin and acetylcholine, decreases neuronal activity by pos-synaptic hyperpolarization and inhibits dopaminergic activity. Adenosine deaminase participates in purine metabolism by converting adenosine into inosine. The most frequent functional polymorphism of adenosine deaminase (22G→A) (ADA1*2) exhibits 20-30% lower enzymatic activity in individuals with the G/A genotype than individuals with the G/G genotype. The aim of this study was to evaluate the ADA polymorphism 22G→A (ADA1*2) in schizophrenic patients and healthy controls. Method: The genotypes of the ADA 22G→A were identified with allele-specific PCR strategy in 152 schizophrenic patients and 111 healthy individuals. Results: A significant decrease in the frequency of the G/A genotype was seen in schizophrenic patients (7/152 -4.6%) relative to controls (13/111 -11.7%, p = 0.032, OR = 2.6). Conclusion: These results suggest that the G/A genotype associated with low adenosine deaminase activity and, supposingly, with higher adenosine levels is less frequent among schizophrenic patients. 7%, p = 0,032,OR = 2,6 Descriptors

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Section: Discussionmentioning

confidence: 65%

Section: Introductionmentioning

confidence: 99%

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confidence: 99%

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Lower frequency of the low activity adenosine deaminase allelic variant (ADA1*2) in schizophrenic patients

Dutra

Ottoni

Lara

et al. 2010

Rev. Bras. Psiquiatr.

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“…The adenosinergic system can affect the efficiency of synaptic transmission and neurotransmitter release through a combined activation of inhibitory adenosine A 1 receptors and facilitatory adenosine A 2A receptors in neuronal circuits [28,29]. There is a growing body of evidence suggesting that these adenosine receptors could be promising therapeutic targets in a wide range of conditions, including neurodegenerative and psychiatric disorders such as major depression [30][31][32][33][34]. However, the interaction between antidepressant compounds and adenosine receptors in the central nervous system remains largely unexplored.…”

Section: Introductionmentioning

confidence: 99%

Creatine, similarly to ketamine, affords antidepressant-like effects in the tail suspension test via adenosine A1 and A2A receptor activation

Cunha

Pazini

Rosa

et al. 2015

Purinergic Signalling

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The benefits of creatine supplementation have been reported in a broad range of central nervous systems diseases, including depression. A previous study from our group demonstrated that creatine produces an antidepressant-like effect in the tail suspension test (TST), a predictive model of antidepressant activity. Since depression is associated with a dysfunction of the adenosinergic system, we investigated the involvement of adenosine A 1 and A 2A receptors in the antidepressant-like effect of creatine in the TST. The anti-immobility effect of creatine (1 mg/kg, po) or ketamine (a fast-acting antidepressant, 1 mg/kg, ip) in the TST was prevented by pretreatment of mice with caffeine (3 mg/kg, ip, nonselective adenosine receptor antagonist), 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) (2 mg/kg, ip, selective adenosine A 1 receptor antagonist), and 4-(2-[7-amino-2-{2-furyl}{1,2,4}triazolo-{2,3-a}{1,3,5}triazin-5-ylamino]ethyl)-phenol (ZM241385) (1 mg/kg, ip, selective adenosine A 2A receptor antagonist). In addition, the combined administration of subeffective doses of creatine and adenosine (0.1 mg/kg, ip, nonselective adenosine receptor agonist) or inosine (0.1 mg/kg, ip, nucleoside formed by the breakdown of adenosine) reduced immobility time in the TST. Moreover, the administration of subeffective doses of creatine or ketamine combined with N-6-cyclohexyladenosine (CHA) (0.05 mg/kg, ip, selective adenosine A 1 receptor agonist), N-6-[2-(3,5-dimethoxyphenyl)-2-(methylphenyl)ethyl]adenosine (DPMA) (0.1 mg/kg, ip, selective adenosine A 2A receptor agonist), or dipyridamole (0.1 μg/mouse, icv, adenosine transporter inhibitor) produced a synergistic antidepressant-like effect in the TST. These results indicate that creatine, similarly to ketamine, exhibits antidepressant-like effect in the TST probably mediated by the activation of both adenosine A 1 and A 2A receptors, further reinforcing the potential of targeting the purinergic system to the management of mood disorders.

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“…Recent reviews have shown that adenosine receptors are related to the pathophysiology of neuropsychiatric disorders and neurodegenerative diseases Jacobson and Gao, 2006). Lara et al (2006) reported the involvement of adenosine in the neurobiology of schizophrenia. Adenosine A1 receptor (ADORA1)-mediated inhibition of dopamine release from rat striatal slices is modulated by D1 dopamine receptor (O'Neill et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

A Polymorphism (rs10920568, A102A) of Adenosine A1 Receptor (ADORA1) Gene is Associated with Schizophrenia in Korean Population

Hong

Kim

et al. 2008

Exp Neurobiol

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Adenosine A1 receptor (ADORA1) has a neuromodulatory activity in early stage of brain development. Recent studies have been suggested that a deficit in adenosinergic function may be a key factor in the pathophysiology of schizophrenia. To determine the genetic association between ADORA1 gene polymorphism and schizophrenia in Korean population, we genotyped single nucleotide polymorphism (SNP) (rs10920568, A102A, exon5) in the ADORA1 gene by using the direct sequencing. Among SNPs in the coding region of ADORA1, only one synonymous SNP's heterozygosity (rs10920568) is more than 0.05. Three hundred three control and 284 schizophrenia subjects were recruited. For the analysis of genetic data, EM algorithm, SNPStats, SNPAnalyzer, and Helixtree programs were used. Multiple logistic regression analysis with the codominant, dominant, and recessive models was performed. The genotype frequencies of rs10920568 showed statistically significant difference between schizophrenic patients and healthy control subjects. The rs10920568 SNP of ADORA1 was weakly associated with schizophrenia in the dominant model (p=0.04, odds ratio=0.70, 95% confidence interval =0.50∼0.98). The result suggests that the ADORA1 gene may be associated with schizophrenia.

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Involvement of adenosine in the neurobiology of schizophrenia and its therapeutic implications

Cited by 129 publications

References 117 publications

Lower frequency of the low activity adenosine deaminase allelic variant (ADA1*2) in schizophrenic patients

Lower frequency of the low activity adenosine deaminase allelic variant (ADA1*2) in schizophrenic patients

Creatine, similarly to ketamine, affords antidepressant-like effects in the tail suspension test via adenosine A1 and A2A receptor activation

A Polymorphism (rs10920568, A102A) of Adenosine A1 Receptor (ADORA1) Gene is Associated with Schizophrenia in Korean Population

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