Modulation of striatal adenosine A1 and A2 receptors induces rotational behaviour in response to dopaminergic stimulation in intact rats

Popoli, Patrizia; Pézzola, Antonella; Carolis, A. Scotti de

doi:10.1016/0014-2999(94)90689-0

Cited by 58 publications

(21 citation statements)

References 24 publications

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“…Nevertheless, we have also demonstrated A 2A -D 2 receptor interactions in the ventral striatum that are similar to interactions in the dorsal striatum (reviewed in Ferré, 1997). At the behavioral level, by acting on the ventral striatum, A 2A receptor agonists counteract and A 2A antagonists potentiate the motor, discriminative and rewarding effects of psychostimulants (Heffner et al, 1989;Popoli et al, 1994;Rimondini et al, 1997;Shimazoe et al, 2000;Knapp et al, 2001;Poleszak and Malec, 2002;Justinova et al, 2003;Filip et al, 2006). The non-selective A 1 and A 2A antagonist caffeine also potentiates these responses to psychostimulants (Misra et al, 1986;Logan et al, 1989;Gauvin et al, 1990;Horger et al, 1991;Comer and Carroll, 1996;Gasior et al, 2000;Munzar et al, 2002).…”

Section: Adenosine a 2a Receptors In The Ventral Striatum And The Acumentioning

confidence: 99%

Adenosine A2A receptors in ventral striatum, hypothalamus and nociceptive circuitry

Ferré

Diamond

Goldberg

et al. 2007

Progress in Neurobiology

127

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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 The Acumentioning

confidence: 99%

Adenosine A2A receptors in ventral striatum, hypothalamus and nociceptive circuitry

Ferré

Diamond

Goldberg

et al. 2007

Progress in Neurobiology

127

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“…Stimulation of adenosine A 2A Rs decreases the binding affinity of D 2 receptors (4) and elicits effects opposite to the ones shown by D 2 receptor activation at the level of second-messenger systems and early gene expression (5,6). These observations suggest that antagonistic adenosine-dopamine interactions may be important in the regulation of the activity of the basal ganglia and could explain the depressant and stimulating effects of adenosine A 2A R agonists and antagonists on motor behavior (7).In addition, adenosine receptor agonists induce sedation and catalepsy dose-dependently and inhibit the motoractivating effects of dopamine receptor agonists (7,8). In contrast, adenosine receptor antagonists, including caffeine and related methylxanthines, produce motor-stimulant effects (9), which appear to be related to an action on A 2A rather than on A 1 receptors (10).…”

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confidence: 99%

“…In addition, adenosine receptor agonists induce sedation and catalepsy dose-dependently and inhibit the motoractivating effects of dopamine receptor agonists (7,8). In contrast, adenosine receptor antagonists, including caffeine and related methylxanthines, produce motor-stimulant effects (9), which appear to be related to an action on A 2A rather than on A 1 receptors (10).…”

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confidence: 99%

Brain Adenosine A_2A Receptor Occupancy by a Novel A₁/A_2A Receptor Antagonist, ASP5854, in Rhesus Monkeys: Relationship to Anticataleptic Effect

Mihara

Noda²,

Arai³

et al. 2008

J Nucl Med

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The purpose of the present study was to measure adenosine A 2A receptor (A 2A R) occupancy in the brain by a novel adenosine A 1 / A 2A antagonist, 5-[5-amino-3-(4fluorophenyl)pyrazin-2-yl]-1-isopropylpyridine-2(1H)-one (ASP5854), and to determine the degree of receptor occupancy necessary to inhibit haloperidolinduced catalepsy in rhesus monkeys. Methods: A 2A R occupancy by ASP5854 (0.001-0.1 mg/kg) was examined in the striatum using an A 2A R-specific radiotracer, 11 C-SCH442416, and PET in conscious rhesus monkeys. A 2A R occupancy was monitored after a single intravenous administration of ASP5854 in 3 animals, and a dynamic PET scan was performed at 1, 4, and 8 h after an intravenous bolus injection of the tracer for approximately 740 MBq. Catalepsy was induced by haloperidol (0.03 mg/kg, intramuscularly) and examined for incidence and duration. Results: ASP5854 dose-dependently increased A 2A R occupancy in the striatum and showed long-lasting occupancy even after the reduction of plasma concentration. Haloperidol induced severe catalepsy at 40 min after intramuscular injection. The incidence and duration of cataleptic posture were dose-dependently reduced by ASP5854 at 1 h after oral administration, and the minimum ED 50 value was 0.1 mg/kg. Administration of a dose of 0.1 mg/kg yielded a plasma concentration of 97 6 16.3 ng/mL, which corresponded to 85%-90% of A 2A R occupancy. Conclusion: These results showed that ASP5854 antagonized A 2A R in the striatum, and the dissociation from A 2A R was relatively slow. In addition, more than 85% A 2A R occupancy by ASP5854 resulted in an inhibition of haloperidol-induced catalepsy. Thus, such a pharmacodynamic study directly demonstrates both the kinetics of a drug in the brain and the relationship between dose-dependent receptor occupancy and plasma level. Adenosi ne A 2A receptors (A 2A Rs) are abundantly localized in the caudate-putamen, nucleus accumbens, and olfactory tubercle in several species (1). They are coexpressed with dopamine D 2 receptors in the GABAergic striatopallidal neurons; in contrast, there are no A 2A Rs in the neurons projecting from the striatum to the substantial nigra and expressing D 1 receptors (2,3). Stimulation of adenosine A 2A Rs decreases the binding affinity of D 2 receptors (4) and elicits effects opposite to the ones shown by D 2 receptor activation at the level of second-messenger systems and early gene expression (5,6). These observations suggest that antagonistic adenosine-dopamine interactions may be important in the regulation of the activity of the basal ganglia and could explain the depressant and stimulating effects of adenosine A 2A R agonists and antagonists on motor behavior (7).In addition, adenosine receptor agonists induce sedation and catalepsy dose-dependently and inhibit the motoractivating effects of dopamine receptor agonists (7,8). In contrast, adenosine receptor antagonists, including caffeine and related methylxanthines, produce motor-stimulant effects (9), which appear to be related to an action on A 2...

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“…In general, stimulation of adenosine receptors counteracts the behavioral effects of dopamine receptor stimulation (Ferré et al, 1997). Accordingly, adenosine receptor agonists counteract, whereas adenosine receptor antagonists potentiate, the pharmacological effects of psychostimulants like cocaine and amphetamines (Heffner et al, 1989;Popoli et al, 1994;Rimondini et al, 1997;Malec, 2000, 2002;Shimazoe et al, 2000;Knapp et al, 2001). Therefore, the discriminative-stimulus effects of cocaine and the analog of d-amphetamine methamphetamine should be altered by agents acting at adenosine receptors.…”

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Involvement of Adenosine A₁ and A_2A Receptors in the Adenosinergic Modulation of the Discriminative-Stimulus Effects of Cocaine and Methamphetamine in Rats

Justinová¹,

Ferré²,

Segal³

et al. 2003

J Pharmacol Exp Ther

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Adenosine, by acting on adenosine A 1 and A 2A receptors, is known to antagonistically modulate dopaminergic neurotransmission. We have recently reported that nonselective adenosine receptor antagonists (caffeine and 3,7-dimethyl-1-propargylxanthine) can partially substitute for the discriminativestimulus effects of methamphetamine. In the present study, by using more selective compounds, we investigated the involvement of A 1 and A 2A receptors in the adenosinergic modulation of the discriminative-stimulus effects of both cocaine and methamphetamine. The effects of the A 1 receptor agonist N 6 -cyclopentyladenosine (CPA; 0.01-0.1 mg/kg) and antagonist 8-cyclopentyl-1,3-dimethylxanthine (CPT; 1.3-23.7 mg/kg) and the A 2A receptor agonist 2-p-(2-carboxyethyl)phenethylamino-5Ј-N-ethylcarboxamidoadenosine hydrochloride (CGS 21680; 0.03-0.18 mg/kg) and antagonist 3-(3-hydroxypropyl)-8-(3-methoxystyryl)-7-methyl-1-propargylxanthin phosphate disodium salt (MSX-3; 1-56 mg/kg) were evaluated in rats trained to discriminate either 1 mg/kg methamphetamine or 10 mg/kg cocaine from saline under a fixed-ratio 10 schedule of food presentation. The A 1 and A 2A receptor antagonists (CPT and MSX-3) both produced high levels of drug-lever selection when substituted for either methamphetamine or cocaine and significantly shifted dose-response curves of both psychostimulants to the left. Unexpectedly, the A 2A receptor agonist CGS 21680 also produced drug-appropriate responding (although at lower levels) when substituted for the cocaine-training stimulus, and both CGS 21680 and the A 1 receptor agonist CPA significantly shifted the cocaine dose-response curve to the left. In contrast, both agonists did not produce significant levels of drug-lever selection when substituted for the methamphetamine-training stimulus and failed to shift the methamphetamine dose-response curve. Therefore, adenosine A 1 and A 2A receptors appear to play important but differential roles in the modulation of the discriminative-stimulus effects of methamphetamine and cocaine.

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Modulation of striatal adenosine A1 and A2 receptors induces rotational behaviour in response to dopaminergic stimulation in intact rats

Cited by 58 publications

References 24 publications

Adenosine A2A receptors in ventral striatum, hypothalamus and nociceptive circuitry

Adenosine A2A receptors in ventral striatum, hypothalamus and nociceptive circuitry

Brain Adenosine A_2A Receptor Occupancy by a Novel A₁/A_2A Receptor Antagonist, ASP5854, in Rhesus Monkeys: Relationship to Anticataleptic Effect

Involvement of Adenosine A₁ and A_2A Receptors in the Adenosinergic Modulation of the Discriminative-Stimulus Effects of Cocaine and Methamphetamine in Rats

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Modulation of striatal adenosine A1 and A2 receptors induces rotational behaviour in response to dopaminergic stimulation in intact rats

Cited by 58 publications

References 24 publications

Adenosine A2A receptors in ventral striatum, hypothalamus and nociceptive circuitry

Adenosine A2A receptors in ventral striatum, hypothalamus and nociceptive circuitry

Brain Adenosine A2A Receptor Occupancy by a Novel A1/A2A Receptor Antagonist, ASP5854, in Rhesus Monkeys: Relationship to Anticataleptic Effect

Involvement of Adenosine A1 and A2A Receptors in the Adenosinergic Modulation of the Discriminative-Stimulus Effects of Cocaine and Methamphetamine in Rats

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Brain Adenosine A_2A Receptor Occupancy by a Novel A₁/A_2A Receptor Antagonist, ASP5854, in Rhesus Monkeys: Relationship to Anticataleptic Effect

Involvement of Adenosine A₁ and A_2A Receptors in the Adenosinergic Modulation of the Discriminative-Stimulus Effects of Cocaine and Methamphetamine in Rats