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Adaptive changes in the expression of central opioid receptors in mice lacking the dopamine D2 receptor gene
1Biochemical Sciences, Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey, UK. lena@unice.fr
Abstract:
On the basis of numerous studies that have described interactions between the dopaminergic and opioidergic systems, we have investigated whether genetic deletion of dopamine D2 receptors (D2R) might influence the expression of central opioid receptors. The levels of mu, delta, kappa and nociceptin opioid peptide receptors were determined in the brains and spinal cords of D2R knockout mice using quantitative autoradiography. The significant changes in opioid receptor binding found in the brains of heterozygous and homozygous mice were mainly restricted to the basal ganglia. In homozygous mice, a down-regulation of mu and delta receptors was observed in the striatal and pallidal areas. This alteration may be an adaptive response to the increase in enkephalin levels previously described in the striatum of these mutant mice. On the contrary, an up-regulation of kappa receptors was found in the striatal and nigral regions and might be related to a change in dynorphin levels. Significant increases in nociceptin receptor binding were also observed in homozygous mice in brain areas involved in motor behavior. At the spinal level, only kappa and nociceptin receptor binding showed significant overall differences between genotypes. The functional consequences of these adaptive changes are discussed in relation to the findings of behavioral and neurochemical studies reported to date in D2R knockout mice.
Insights
Genetic deletion of dopamine D2 receptors (D2R) in mice alters central opioid receptor expression, particularly in the basal ganglia. These changes in mu, delta, kappa, and nociceptin receptors may be adaptive responses to neurochemical shifts.
Area of Science:
- Neuroscience
- Pharmacology
- Genetics
Background:
- The dopaminergic and opioidergic systems are known to interact.
- Dopamine D2 receptors (D2R) play a crucial role in modulating neurotransmitter release.
- Understanding these interactions is key to deciphering complex neurological processes.
Purpose of the Study:
- To investigate the impact of dopamine D2 receptor (D2R) genetic deletion on central opioid receptor expression.
- To determine the specific changes in mu, delta, kappa, and nociceptin opioid receptors in D2R knockout mice.
- To explore the adaptive significance of these alterations in relation to known neurochemical changes.
Main Methods:
- Utilized quantitative autoradiography to measure opioid receptor binding.
- Analyzed brains and spinal cords from heterozygous and homozygous D2R knockout mice.
- Compared receptor binding levels across different genotypes and brain regions.
Main Results:
- Significant alterations in opioid receptor binding were observed, primarily in the basal ganglia of D2R knockout mice.
- Homozygous mice showed down-regulation of mu and delta receptors in striatal and pallidal areas.
- Up-regulation of kappa receptors in striatal and nigral regions and increased nociceptin receptor binding in motor areas were noted.
- Spinal cord analysis revealed significant differences in kappa and nociceptin receptor binding between genotypes.
Conclusions:
- Genetic deletion of dopamine D2 receptors induces significant, region-specific adaptive changes in central opioid receptor expression.
- Observed alterations in mu, delta, and kappa receptors correlate with known changes in enkephalin and dynorphin levels.
- These neurochemical adaptations in D2R knockout mice likely have functional consequences on motor behavior and other neurological functions.
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