In:
The Journal of Neuroscience, Society for Neuroscience, Vol. 21, No. 12 ( 2001-06-15), p. 4390-4399
Abstract:
In the striatum, dopamine D 1 and adenosine A 2A receptors stimulate the production of cAMP, which is involved in neuromodulation and long-lasting changes in gene expression and synaptic function. Positive coupling of receptors to adenylyl cyclase can be mediated through the ubiquitous GTP-binding protein Gα S subunit or through the olfactory isoform, Gα olf , which predominates in the striatum. In this study, using double in situ hybridization, we show that virtually all striatal efferent neurons, identified by the expression of preproenkephalin A, substance P, or D 1 receptor mRNA, contained high amounts of Gα olf mRNA and undetectable levels of Gα s mRNA. In contrast, the large cholinergic interneurons contained both Gα olf and Gα s transcripts. To assess the functional relationship between dopamine or adenosine receptors and G-proteins, we examined G-protein levels in the striatum of D 1 and A 2A receptor knock-out mice. A selective increase in Gα olf protein was observed in these animals, without change in mRNA levels. Conversely, Gα olf levels were decreased in animals lacking a functional dopamine transporter. These results indicate that Gα olf protein levels are regulated through D 1 and A 2A receptor usage. To determine the functional consequences of changes in Gα olf levels, we used heterozygous Gα olf knock-out mice, which possess half of the normal Gα olf levels. In these animals, the locomotor effects of amphetamine and caffeine, two psychostimulant drugs that affect dopamine and adenosine signaling, respectively, were markedly reduced. Together, these results identify Gα olf as a critical and regulated component of both dopamine and adenosine signaling.
Type of Medium:
Online Resource
ISSN:
0270-6474
,
1529-2401
DOI:
10.1523/JNEUROSCI.21-12-04390.2001
Language:
English
Publisher:
Society for Neuroscience
Publication Date:
2001
detail.hit.zdb_id:
1475274-8
detail.hit.zdb_id:
604637-X
SSG:
12
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