Characterisation of central adenosine A1 receptors and adenosine transporters in mice lacking the adenosine A2a receptor

Snell, Broughton J.; Short, Jennifer Lynn; Drago, John; Ledent, Catherine; Lawrence, Andrew J

doi:10.1016/s0006-8993(00)02670-6

Cited by 20 publications

(21 citation statements)

References 29 publications

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“…Wild-type mice used in the study were obtained from litters generated by heterozygous breeders. Mice were backcrossed for eight generations and were genotyped by routine PCR (Snell et al, 2000). All experiments were performed with adult male mice housed at the Integrative Neuroscience Facility, Howard Florey Institute.…”

Section: Animalsmentioning

confidence: 99%

A Differential Role for the Adenosine A2A Receptor in Opiate Reinforcement vs Opiate-Seeking Behavior

Brown

Short²,

Cowen

et al. 2008

Neuropsychopharmacol

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The adenosine A 2A receptor is specifically enriched in the medium spiny neurons that make up the 'indirect' output pathway from the ventral striatum, a structure known to have a crucial, integrative role in processes such as reward, motivation, and drug-seeking behavior. In the present study we investigated the impact of adenosine A 2A receptor deletion on behavioral responses to morphine in a number of reward-related paradigms. The acute, rewarding effects of morphine were evaluated using the conditioned place preference paradigm. Operant self-administration of morphine on both fixed and progressive ratio schedules as well as cue-induced drug-seeking was assessed. In addition, the acute locomotor response to morphine as well as sensitization to morphine was evaluated. Decreased morphine selfadministration and breakpoint in A 2A knockout mice was observed. These data support a decrease in motivation to consume the drug, perhaps reflecting diminished rewarding effects of morphine in A 2A knockout mice. In support of this finding, a place preference to morphine was not observed in A 2A knockout mice but was present in wild-type mice. In contrast, robust cue-induced morphine-seeking behavior was exhibited by both A 2A knockout and wild-type mice after a period of withdrawal. The acute locomotor response to morphine in the A 2A knockout was similar to wild-type mice, yet A 2A knockout mice did not display tolerance to chronic morphine under the present paradigm. Both genotypes display locomotor sensitization to morphine, implying a lack of a role for the A 2A receptor in the drug-induced plasticity necessary for the development or expression of sensitization. Collectively, these data suggest a differential role for adenosine A 2A receptors in opiate reinforcement compared to opiate-seeking.

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Section: Animalsmentioning

confidence: 99%

A Differential Role for the Adenosine A2A Receptor in Opiate Reinforcement vs Opiate-Seeking Behavior

Brown

Short²,

Cowen

et al. 2008

Neuropsychopharmacol

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“…Equal numbers of male and female mice from each genotype were assessed for all behavioral experiments. The genotype of experimental mice was confirmed as previously described (Drago et al, 1994;Snell et al, 2000). Mice received laboratory chow and water ad libitum, and were kept in a constant 12-h light-dark cycle (light 0700-1900 hours).…”

Section: Experimental Animalsmentioning

confidence: 99%

Receptor Crosstalk: Characterization of Mice Deficient in Dopamine D1 and Adenosine A2A Receptors

Short

Ledent

Drago

et al. 2005

Neuropsychopharmacol

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Here we report the development of D 1 A 2A receptor knockout mice to investigate whether interactions between dopamine D 1 and adenosine A 2A receptors participate in reward-related behavior. The combined deletion of D 1 and A 2A receptors resulted in mice with decreased weight and appetitive processes, reduced rearing and exploratory behaviors, increased anxiety, and a significantly poorer performance on the rotarod, compared to wild-type littermates. D 1 A 2A receptor knockout mice shared phenotypic similarities with mice deficient in D 1 receptors, while also paralleling behavioral deficits seen in A 2A receptor knockout mice, indicating individual components of the behavioral phenotype of the D 1 A 2A receptor knockout attributable to the loss of both receptors. In contrast, ethanol and saccharin preference in D 1 A 2A receptor knockout mice were distinctly different from that observed in derivative D 1 or A 2A receptordeficient mice. Compared to wild types, preference and consumption of ethanol were decreased in D 1 A 2A receptor knockout mice, the reduction in ethanol consumption greater even than that seen in D 1 receptor-deficient mice. Preference and consumption of saccharin were also reduced in D 1 A 2A receptor knockout mice, whereas saccharin preference was similar in wild-type, D 1 , and A 2A receptor knockout mice. These data suggest an interaction of D 1 and A 2A receptors in the reinforcement processes underlying the intake of rewarding substances, whereby the A 2A receptor seems involved in goal-directed behavior and the motor functions underlying the expression of such behaviors, and the D 1 receptor is confirmed as essential in mediating motivational processes related to the repeated intake of novel substances and drugs.

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“…Recently, cloning studies have revealed the existence of subtypes of A2 receptors (A2a and A2b) and also A3 receptors (Snell et al 2000, d'Alcantara et al 2001, Talukder et al 2002. The surface receptors for adenosine, with the exception of A3 receptors, are antagonized by methylxanthines (van Gallen et al 1994, Klinger et al 2002, while the actions via ''P'' sites are blocked by adenosine transport inhibitors.…”

Section: Introductionmentioning

confidence: 99%

Adenosine as a signaling molecule in the retina: biochemical and developmental aspects

Paes‐de‐Carvalho¹

2002

An. Acad. Bras. Ciênc.

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The nucleoside adenosine plays an important role as a neurotransmitter or neuromodulator in the central nervous system, including the retina. In the present paper we review compelling evidence showing that adenosine is a signaling molecule in the developing retina. In the chick retina, adenosine transporters are present since early stages of development before the appearance of adenosine A1 receptors modulating dopamine-dependent adenylate cyclase activity orA2 receptors that directly activate the enzyme. Experiments using retinal cell cultures revealed that adenosine is taken up by specific cell populations that when stimulated by depolarization or neurotransmitters such as dopamine or glutamate, release the nucleoside through calciumdependent transporter-mediated mechanisms. The presence of adenosine in the extracellular medium and the long-term activation of adenosine receptors is able to regulate the survival of retinal neurons and blocks glutamate excitoxicity. Thus, adenosine besides working as a neurotransmitter or neuromodulator in the mature retina, is considered as an important signaling molecule during retinal development having important functions such as regulation of neuronal survival and differentiation.

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Characterisation of central adenosine A1 receptors and adenosine transporters in mice lacking the adenosine A2a receptor

Cited by 20 publications

References 29 publications

A Differential Role for the Adenosine A2A Receptor in Opiate Reinforcement vs Opiate-Seeking Behavior

A Differential Role for the Adenosine A2A Receptor in Opiate Reinforcement vs Opiate-Seeking Behavior

Receptor Crosstalk: Characterization of Mice Deficient in Dopamine D1 and Adenosine A2A Receptors

Adenosine as a signaling molecule in the retina: biochemical and developmental aspects

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