Adenosine A2A Agonists: A Potential New Type of Atypical Antipsychotic

Rimondini, R

doi:10.1016/s0893-133x(97)00033-x

Cited by 143 publications

(97 citation statements)

References 50 publications

(75 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The dose range of CGS-21680 used also reduces alcohol drinking in mice (Nam et al, 2013), implying a relationship between circadian rhythm improvement and decreased drinking. Similar to several studies (Houchi et al, 2013;Jones et al, 2012;Knapp et al, 2001;Rimondini et al 1997), we observed that CGS-21680 reduced locomotor activity. Alpha (active-phase duration) was reduced in CGS-21680-treated mice of both genotypes vs vehicle-treated WT controls (Figure 4d).…”

Section: Discussionsupporting

confidence: 91%

Adenosinergic Regulation of Striatal Clock Gene Expression and Ethanol Intake During Constant Light

Ruby

Vadnie

Hinton

et al. 2014

Neuropsychopharmacol

View full text Add to dashboard Cite

Circadian rhythm and sleep disruptions occur frequently in individuals with alcohol use disorders (AUD) and present significant barriers to treatment. Recently, a variant of adenosine transporter, equilibrative nucleoside transporter 1 (ENT1), was associated with the cooccurrence of sleep problems and AUD. We have previously shown that mice lacking ENT1 (ENT1 KO) have reduced adenosine levels in the striatum and drink more alcohol compared with wild types (WT). However, it is unknown whether ENT1 deletion disrupts circadian rhythms, which may contribute to alcohol preference in ENT1 KO mice. Here we used these mice to determine whether endogenous adenosine regulates circadian genetic and behavioral rhythms and influences alcohol intake during chronodisruption. We examined circadian locomotor activity in ENT1 KO vs WT littermates and found that ENT1 KO mice were both active earlier and hyperactive compared with WT mice at night. We used real-time PCR and immunohistochemistry to estimate striatal clock gene levels and found that PER2 expression in the striatum was blunted by ENT1 deletion or A2A receptor (A2AR) antagonism. Next, we exposed ENT1 KO and WT mice to constant light (LL) and found further elevation in ethanol intake in ENT1 KO, but not in WT mice, supporting the notion that circadian dysfunction may contribute to increased alcohol intake in ENT1 KO mice. Finally, we showed that A2AR agonist administration normalized PER1 and PER2 expression and circadian locomotor activity in ENT1 KO mice. Together, our results demonstrate that adenosine signaling regulates cellular and behavioral circadian timing and influences alcohol intake during chronodisruption.

show abstract

Section: Discussionsupporting

confidence: 91%

Adenosinergic Regulation of Striatal Clock Gene Expression and Ethanol Intake During Constant Light

Ruby

Vadnie

Hinton

et al. 2014

Neuropsychopharmacol

View full text Add to dashboard Cite

show abstract

“…Consistent with these previous findings of an interaction between DA and adenosine receptors, adenosine A 2A agonists have been shown to induce effects that resemble those produced by DA antagonists or DA depletions (Heffner et al 1989;Barraco et al 1993;Ferré 1997;Rimondini et al 1997). Administration of the adenosine A 2A receptor agonist CGS 21680 into the ventricles inhibited acquisition and expression of wheel running behavior (Cabeza de Vaca et al 2007).…”

Section: Introductionsupporting

confidence: 84%

Intra-accumbens injections of the adenosine A2A agonist CGS 21680 affect effort-related choice behavior in rats

et al. 2008

View full text Add to dashboard Cite

Rationale-Nucleus accumbens dopamine (DA) participates in the modulation of instrumental behavior, including aspects of behavioral activation and effort-related choice behavior. Rats with impaired accumbens DA transmission reallocate their behavior away from food-reinforced activities that have high response requirements and instead select less-effortful types of food-seeking behavior. Although accumbens DA is considered a critical component of the brain circuitry regulating effortrelated processes, emerging evidence also implicates adenosine A 2A receptors.Objective-The present work was undertaken to test the hypothesis that accumbens A 2A receptor stimulation would produce effects similar to those produced by DA depletion or antagonism.Materials and methods-Three experiments assessed the effects of the adenosine A 2A agonist CGS 21680 on performance of a concurrent choice task (lever pressing for preferred food vs. intake of less preferred chow) that is known to be sensitive to DA antagonists and accumbens DA depletions.Results-Systemic injections of CGS 21680 reduced lever pressing but did not increase feeding. In contrast, bilateral infusions of the adenosine A 2A receptor agonist CGS 21680 (6.0-24.0 ng) into the nucleus accumbens decreased lever pressing for the preferred food but substantially increased consumption of the less preferred chow. Injections of CGS 21680 into a control site dorsal to the accumbens were ineffective.Conclusions-Taken together, these results are consistent with the hypothesis that local stimulation of adenosine A 2A receptors in nucleus accumbens produces behavioral effects similar to those induced by accumbens DA depletions. Accumbens adenosine A 2A receptors appear to be a component of the brain circuitry regulating effort-related choice behavior.

show abstract

“…Similarly, using BRET methodology, cocaine was shown, through direct actions on D2R, to induce a conformational change in the A2-D2 complex, resulting in reduced BRETmax, potentially indicative of a reduction in heteromer expression . In schizophrenia animal models, evidence of antipsychotic effects of the A2 receptor (A2R) agonist CGS 21680 have been demonstrated (Andersen et al, 2002;Rimondini et al, 1997), and adenosine augmentation has been shown to ameliorate both psychotic and cognitive schizophrenia-like symptoms in mice , potentially by acting at the A2R within the A2-D2 heteromer, and thus reducing the proportion of D2R in the agonist-induced high-affinity state and D2R signaling Fuxe et al, 2010). It has been further suggested that an imbalance in adenosine signaling, a neurotransmitter which modulates both dopamine and glutamate transmission, may be a central factor in the susceptibility to develop schizophrenia (Boison et al, 2012).…”

Section: Adenosine-dopamine Receptor Heteromers: A1-d1 A2-d2mentioning

confidence: 99%

Heteromeric Dopamine Receptor Signaling Complexes: Emerging Neurobiology and Disease Relevance

Perreault

Hasbi

O’Dowd

et al. 2013

Neuropsychopharmacol

138

107

View full text Add to dashboard Cite

The pharmacological modification of dopamine transmission has long been employed as a therapeutic tool in the treatment of many mental health disorders. However, as many of the pharmacotherapies today are not without significant side effects, or they alleviate only a particular subset of symptoms, the identification of novel therapeutic targets is imperative. In light of these challenges, the recognition that dopamine receptors can form heteromers has significantly expanded the range of physiologically relevant signaling complexes as well as potential drug targets. Furthermore, as the physiology and disease relevance of these receptor heteromers is further understood, their ability to exhibit pharmacological and functional properties distinct from their constituent receptors, or modulate the function of endogenous homomeric receptor complexes, may allow for the development of alternate therapeutic strategies and provide new avenues for drug design. In this review, we describe the emerging neurobiology of the known dopamine receptor heteromers, their physiological relevance in brain, and discuss the potential role of these receptor complexes in neuropsychiatric disease. We highlight their value as targets for future drug development and discuss innovative research strategies designed to selectively target these dopamine receptor heteromers in the search for novel and clinically efficacious pharmacotherapies.

show abstract

Adenosine A2A Agonists: A Potential New Type of Atypical Antipsychotic

Cited by 143 publications

References 50 publications

Adenosinergic Regulation of Striatal Clock Gene Expression and Ethanol Intake During Constant Light

Adenosinergic Regulation of Striatal Clock Gene Expression and Ethanol Intake During Constant Light

Intra-accumbens injections of the adenosine A2A agonist CGS 21680 affect effort-related choice behavior in rats

Heteromeric Dopamine Receptor Signaling Complexes: Emerging Neurobiology and Disease Relevance

Contact Info

Product

Resources

About