Elsevier

Neuroscience

Volume 139, Issue 2, 2006, Pages 661-670
Neuroscience

Neuropharmacology
Genetic interdependence of adenosine and dopamine receptors: Evidence from receptor knockout mice

https://doi.org/10.1016/j.neuroscience.2005.12.052Get rights and content

Abstract

Dopamine and adenosine receptors are known to share a considerable overlap in their regional distribution, being especially rich in the basal ganglia. Dopamine and adenosine receptors have been demonstrated to exhibit a parallel distribution on certain neuronal populations, and even when not directly co-localized, relationships (both antagonistic and synergistic) have been described. This study was designed to investigate dopaminergic and purinergic systems in mice with ablations of individual dopamine or adenosine receptors. In situ hybridization histochemistry and autoradiography was used to examine the level of mRNA and protein expression of specific receptors and transporters in dopaminergic pathways. Expression of the mRNA encoding the dopamine D2 receptor was elevated in the caudate putamen of D1, D3 and A2A receptor knockout mice; this was mirrored by an increase in D2 receptor protein in D1 and D3 receptor knockout mice, but not in A2A knockout mice. Dopamine D1 receptor binding was decreased in the caudate putamen, nucleus accumbens, olfactory tubercle and ventral pallidum of D2 receptor knockout mice. In substantia nigra pars compacta, dopamine transporter mRNA expression was dramatically decreased in D3 receptor knockout mice, but elevated in A2A receptor knockout mice. All dopamine receptor knockout mice examined exhibited increased A2A receptor binding in the caudate putamen, nucleus accumbens and olfactory tubercle. These data are consistent with the existence of functional interactions between dopaminergic and purinergic systems in these reward and motor-related brain regions.

Section snippets

Experimental procedures

All experiments were performed in accordance with the Prevention of Cruelty to Animals Act 1986, under the guidelines of the Australian National Health and Medical Research Council Code of Practice for the Care and Use of Animals for Experimental Purposes in Australia. Formal approval for all experiments was granted by the Department of Pharmacology Animal Ethics Committee (Monash University). All efforts were made to minimize the number of animals used and their suffering, and all experiments

Dopamine D1 receptors

D1 receptor mRNA was detected in the CPu, NAcc and OT in all mice examined other than D1 receptor knockout mice. The addition of a 100-fold excess of unlabeled oligonucleotide completely abolished the hybridization signal. The hybridization signal in D1 receptor knockout mice resembled that of non-specific background. No differences in the level of D1 mRNA were found between D2 or D3 receptor knockout and wild-type mice (data not shown). D1 receptor mRNA was elevated in the CPu and NAcc of A2A

Discussion

While some studies have examined the mRNA expression and binding of various dopamine receptors in mice with specific deletions of dopamine receptor subtypes (e.g. Baik et al 1995, Accili et al 1996, Wong et al 2003), few studies have compared the expression of adenosine receptors in dopamine receptor knockout mice, and vice versa. Moreover, no study has previously interrogated these systems in a complementary and concurrent manner to examine dopamine D1 and D2 receptor expression in adenosine A

Acknowledgments

This work was supported by the National Health and Medical Research Council of Australia (program grant 236805) of which A.J.L. is a Senior Research Fellow and J.D. a Practitioner Fellow.

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