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Journal of Neuroscience, Vol 13, 1080-1087, Copyright © 1993 by Society for Neuroscience
Adenosine A2 receptors regulate the gene expression of striatopallidal and striatonigral neurons
SN Schiffmann and JJ Vanderhaeghen
Laboratory of Neurophysiology, Neuropathology and Neuropeptide Research, Erasme Hospital, Faculty of Medicine, Universite Libre de Bruxelles, Belgium.
Adenosine acts as a neuromodulator through A1 and A2 receptors. The
adenosine analogs have been recognized, among other effects, as strong
depressors of the locomotor activity by acting on striatal A2 receptors.
Moreover, the A2a receptor subtype is exclusively expressed in the
striatum. To elucidate at the cellular level the roles of adenosine in the
basal ganglia, the anatomical and functional relationships of the A2
receptors with the dopamine D1 and D2 receptors were studied in the rat
striatum. In situ hybridization histochemistry was used either in
combination with retrograde labeling of striatonigral neurons to determine
the projection site of A2a receptor expressing neurons, or on consecutive
thin sections to address the putative coexpression of the A2a receptor with
the D1 or D2 receptors in individual neurons. The A2a receptor is mainly
expressed by neurons projecting to the globus pallidus and expressing also
the dopamine D2 receptor and enkephalin, but very sparsely by neurons
projecting to the substantia nigra that express the dopamine D1 receptor
and substance P. We have further examined the regulatory effect of the A2
receptors on striatal gene expression using in situ hybridization
histochemistry and quantitative autoradiography. Rats unilaterally depleted
in dopamine by an unilateral 6-hydroxydopamine-induced lesion of the
nigrostriatal pathway used as a model of Parkinson's disease subsequently
received chronic injections of saline or the adenosine receptor antagonist
caffeine. Intact rats were chronically treated with either saline, caffeine
alone, caffeine with N-ethyl-carboxamidoadenosine (an equipotent A1 and A2
agonist), or caffeine with cyclohexyladenosine (a more selective A1
agonist).(ABSTRACT TRUNCATED AT 250 WORDS)
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