Trends in Neurosciences
Volume 20, Issue 10, 1 October 1997, Pages 482-487
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Adenosine–dopamine receptor–receptor interactions as an integrative mechanism in the basal ganglia

https://doi.org/10.1016/S0166-2236(97)01096-5Get rights and content

Abstract

Increasing evidence suggests that antagonistic interactions between specific subtypes of adenosine and dopamine receptors in the basal ganglia are involved in the motor depressant effects of adenosine receptor agonists and the motor stimulant effects of adenosine receptor antagonists, such as caffeine. The GABAergic striatopallidal neurons are regulated by interacting adenosine A2A and dopamine D2 receptors. On the other hand, the GABAergic striatonigral and striatoentopeduncular neurons seem to be regulated by interacting adenosine A1 and dopamine D1 receptors. Furthermore, behavioural studies have revealed interactions between adenosine A2A and dopamine D1 receptors that occur at the network level. These adenosine–dopamine receptor–receptor interactions might offer new therapeutic leads for basal ganglia disorders.

Section snippets

Localization of dopamine and adenosine receptors in the basal ganglia

The striatum (morphologically divided into caudate–putamen, nucleus accumbens and olfactory tubercle) receives glutamatergic inputs from cortical, cortical-like and thalamic areas2, 3. Most striatal neurons (more than 90%) are GABAergic medium-sized spiny neurons and the second most abundant striatal neuron is the large cholinergic aspiny interneuron (about 5%). There are two subtypes of striatal GABAergic efferent neurons: striatopallidal neurons, which contain the peptide enkephalin and

Interactions between adenosine and dopamine receptors at the cellular level

There is evidence that the binding characteristics to one type of G-protein-coupled receptor can be altered by the stimulation of another type of G-protein-coupled receptor in crude membrane preparations[22]. These intramembrane interactions have been postulated as direct interactions between the receptor molecules or to involve G proteins or other mobile molecules associated with the membrane[22]. In particular, in the rat striatal membranes, the stimulation of A1 and A2A receptors

Interactions between adenosine and dopamine receptors at the level of neuronal function

By using in vivo microdialysis it has been shown that the infusion of the A2A agonist CGS 21680 in the caudate–putamen completely counteracts a D2 receptor agonist-induced decrease in extracellular GABA levels in the ipsilateral globus pallidus[39]. Conversely, the striatal infusion of a low concentration of the adenosine receptor antagonist theophylline, which did not by itself modify the extracellular levels of dopamine in the striatum or of GABA in the globus pallidus, did in fact potentiate

Interactions between adenosine and dopamine receptors at the behavioural level

The basal ganglia are components of cortico–subcortical circuits involved in the parallel processing of information related to the performance and learning of motor acts. Direct and indirect efferent pathways connect the striatum with the output structures of the basal ganglia1, 2(Fig. 1). The direct pathway consists of the striatonigral and striato–entopeduncular neurons, while the striatopallidal neurons give rise to the indirect pathway. The most accepted model of basal ganglia circuitry

Acknowledgements

Graphic design is by Teresa Guix. This work is supported by a coordinated European BIOMED 2 project (BM4-CT96-0238).

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