Stimulation of Adenosine Receptors Selectively Activates Gene Expression in Striatal Enkephalinergic Neurons

Karcz-Kubicha, Marzena; Ferré, Sergi; Diaz-Ruiz, Oscar; Quiroz-Molina, César; Goldberg, Steven R.; Hope, Bruce T.; Morales, Marisela

doi:10.1038/sj.npp.1301035

Cited by 22 publications

(17 citation statements)

References 42 publications

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“…The relative efficacy of the combined stimulation of A 2A and A 1 receptors compared to A 2A alone may be explained by the results reported by Karcz-Kubicha et al [23, 24]. In this work, administration of an A 1 or A 2A receptor agonist alone did not induce striatal c-Fos expression.…”

Section: Discussionsupporting

confidence: 56%

“…Karcz-Kubicha et al [23, 24] reported that administration of an A 2A agonist alone failed to induce c-Fos in the striatum, whereas co-administration of the same A 2A agonist plus an A 1 agonist resulted in significant increase in striatal c-Fos expression as well as enkephalin expression. Importantly, this increased expression was observed in striatopallidal but not striatonigral neurons.…”

Section: Introductionmentioning

confidence: 99%

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Indirect basal ganglia pathway mediation of repetitive behavior: Attenuation by adenosine receptor agonists

Tanimura

Vaziri

Lewis

2010

Behavioural Brain Research

112

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Repetitive behaviors are diagnostic for autism and common in related neurodevelopmental disorders. Despite their clinical importance, underlying mechanisms associated with the expression of these behaviors remain poorly understood. Our lab has previously shown that the rates of spontaneous stereotypy in deer mice (Peromyscus maniculatus) were negatively correlated with enkephalin content, a marker of striatopallidal but not striatonigral neurons. To investigate further the role of the indirect basal ganglia pathway, we examined neuronal activation of the subthalamic nucleus (STN) using cytochrome oxidase (CO) histochemistry in high and low stereotypy mice. CO activity in STN was significantly lower in high stereotypy mice and negatively correlated with the frequency of stereotypy. In addition, exposure to environmental enrichment, which attenuated stereotypy, normalized the activity of STN. Co-administration of the adenosine A 2A receptor agonist CGS21680 and the A 1 receptor agonist CPA attenuated stereotypy dose-dependently. The significant reduction associated with the lowest dose of the drug combination tested was due to its effects on mice with lower baseline levels of stereotypy seen. Higher doses of the drug combination were required to show robust behavioral effects, and presumably requisite activation of the indirect pathway, in highstereotypy mice. These findings support that decreased indirect pathway activity is linked to the expression of high levels of stereotypy in deer mice and that striatal A 1 and A 2A receptors may provide promising therapeutic targets for the treatment of repetitive behaviors in neurodevelopmental disorders.

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Section: Discussionsupporting

confidence: 56%

Section: Introductionmentioning

confidence: 99%

Indirect basal ganglia pathway mediation of repetitive behavior: Attenuation by adenosine receptor agonists

Tanimura

Vaziri

Lewis

2010

Behavioural Brain Research

112

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“…The main projection target of the direct pathway is the VTA, whereas the indirect pathway targets the ventral pallidum (Aubert et al, 2000;Steiner and Gerfen, 1998). Stimulation of A 2A receptors activates enkephalin-containing neurons in the striatum, which form the indirect pathway (Karcz-Kubicha et al, 2006;Svenningsson et al, 1999a), while stimulation of D 2 receptors inhibits activity at these same neurons (Svenningsson et al, 1999a). Decreased GABA release in the ventral pallidum is associated with cocaine seeking (Tang et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

Adenosine A2A Receptors in the Nucleus Accumbens Bi-Directionally Alter Cocaine Seeking in Rats

O’Neill

LeTendre

Bachtell

2011

Neuropsychopharmacol

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Repeated cocaine administration enhances dopamine D(2) receptor sensitivity in the mesolimbic dopamine system, which contributes to drug relapse. Adenosine A(2A) receptors are colocalized with D(2) receptors on nucleus accumbens (NAc) medium spiny neurons where they antagonize D(2) receptor activity. Thus, A(2A) receptors represent a target for reducing enhanced D(2) receptor sensitivity that contributes to cocaine relapse. The aim of these studies were to determine the effects of adenosine A(2A) receptor modulation in the NAc on cocaine seeking in rats that were trained to lever press for cocaine. Following at least 15 daily self-administration sessions and 1 week of abstinence, lever pressing was extinguished in daily extinction sessions. We subsequently assessed the effects of intra-NAc core microinjections of the A(2A) receptor agonist, CGS 21680 (4-[2-[[6-amino-9-(N-ethyl-b-D-ribofuranuronamidosyl)-9H-purin-2-yl]amino]ethyl]benzenepropanoic acid hydrochloride), and the A(2A) receptor antagonist, MSX-3 (3,7-dihydro-8-[(1E)-2-(3-methoxyphenyl)ethenyl]-7-methyl-3-[3-(phosphonooxy)propyl-1-(2-propynyl)-1H-purine-2,6-dione disodium salt hydrate), in modulating cocaine- and quinpirole-induced reinstatement to cocaine seeking. Intra-NAc pretreatment of CGS 21680 reduced both cocaine- and quinpirole-induced reinstatement. These effects were specific to cocaine reinstatement as intra-NAc CGS 21680 had no effect on sucrose seeking in rats trained to self-administer sucrose pellets. Intra-NAc treatment with MSX-3 modestly reinstated cocaine seeking when given alone, and exacerbated both cocaine- and quinpirole-induced reinstatement. Interestingly, the exacerbation of cocaine seeking produced by MSX-3 was only observed at sub-threshold doses of cocaine and quinpirole, suggesting that removing tonic A(2A) receptor activity enables behaviors mediated by dopamine receptors. Taken together, these findings suggest that A(2A) receptor stimulation reduces, while A(2A) blockade amplifies, D(2) receptor signaling in the NAc that mediates cocaine relapse.

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“…Stimulation of the adenosine A 2A receptors is known to activate dopamine D 2 - and enkephalin-containing neurons in the striatum that form the indirect pathway (Karcz-Kubicha et al 2006). Thus, local stimulation of A 2A receptors in the dorsal and ventral striatum enhances GABA input to the globus pallidus and ventral pallidum, respectively (Mingote et al 2008; Ochi et al 2000).…”

Section: Discussionmentioning

confidence: 99%

Effects of adenosine A2A receptor stimulation on cocaine-seeking behavior in rats

Bachtell

Self

2009

Psychopharmacology

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Rationale Dopamine (DA) receptor stimulation in the nucleus accumbens (NAc) plays an important role in regulating cocaine–seeking behavior. Adenosine receptors antagonize the effects of DA receptor stimulation on intracellular signaling, neuronal output and behavior. Objectives The goal of the present study is to determine the effects of adenosine A2A receptor stimulation on reinstatement of cocaine-seeking behavior in rats. Methods Rats were trained to lever press for cocaine in daily self-administration sessions on a fixed-ratio 1 schedule for 3 weeks. After one week of abstinence, lever pressing was extinguished in 6 daily extinction sessions. We subsequently assessed the effects of the adenosine A2A receptor agonist, CGS 21680, on cocaine-, quinpirole (D2 agonist)- and cue-induced reinstatement to cocaine seeking. We also assessed the effects of CGS 21680 on sucrose seeking in rats extinguished from sucrose self-administration. Results Pretreatment of CGS 21680 dose-dependently blunted cocaine-induced reinstatement (15 mg/kg, i.p.). Pretreatment with CGS 21680 (0.03 mg/kg, i.p.) also attenuated quinpirole- and cue-induced reinstatement. A minimally effective dose of CGS 21680 failed to alter cocaine-induced locomotor activity or sucrose seeking. Conclusions Stimulation of adenosine A2A receptors antagonizes reinstatement of cocaine seeking elicited by cocaine, DA D2-receptor stimulation and cocaine-conditioned cues. These findings suggest that adenosine A2A receptor stimulation may oppose DA D2 receptor signaling in the NAc that mediates cocaine relapse.

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Stimulation of Adenosine Receptors Selectively Activates Gene Expression in Striatal Enkephalinergic Neurons

Cited by 22 publications

References 42 publications

Indirect basal ganglia pathway mediation of repetitive behavior: Attenuation by adenosine receptor agonists

Indirect basal ganglia pathway mediation of repetitive behavior: Attenuation by adenosine receptor agonists

Adenosine A2A Receptors in the Nucleus Accumbens Bi-Directionally Alter Cocaine Seeking in Rats

Effects of adenosine A2A receptor stimulation on cocaine-seeking behavior in rats

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