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Exploration of sex differences in Rhes effects in dopamine mediated behaviors

By Gabriel C Quintero and Daniela Spano


Studies have shown that Ras homolog enriched in striatum (Rhes) proteins are highly expressed in areas of the central nervous system that have high dopaminergic innervation. In this study, we used Rhes mutant mice (Wild type, Rhes KO, Rhes Heterozygous) of both sexes to explore differences in the effects of Rhes protein levels in basal levels of activity, anxiety, and stereotypy, in relation to sex. Adult male and female mice were evaluated in an open field test for measuring basal levels of activity and anxiety for 5 consecutive days, and they were tested in the apomorphine-induced stereotypy paradigm. Rhes protein levels affected basal levels of activity but it was not found to be related to sex differences. Moreover, a decrease in Rhes protein levels was linked to a nonsignificant anxiolytic effect, mainly in female mice. Finally, a decrease in Rhes protein levels does not affect dopamine D1 and D2 receptor (D1/D2) synergism in female or male mice. Together, these results suggest that Rhes protein levels affect locomotion activity, and have an influence in anxiety depending on sex; Rhes protein levels do not affect D1/D2 synergism in both sexes

Topics: Original Research
Publisher: Dove Medical Press
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Provided by: PubMed Central

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  1. A prompt emergency hypnotic.
  2. Activation of heterotrimeric G-protein signaling by a ras-related protein. Implications for signal integration.
  3. Apomorphine and psychopathology.
  4. Behavioral synergism between D(1) and D(2) dopamine receptors in mice does not depend on gap junctions.
  5. Clinical studies with dopamine-receptor stimulants.
  6. D1 dopamine receptor activation required for postsynaptic expression of D2 agonist effects.
  7. Delirium tremens.
  8. Dexras1/AGS-1 inhibits signal transduction from the Gi-coupled formyl peptide receptor to Erk-1/2 MAP kinases.
  9. (1984). Differential inhibition by dopamine D-1 and D-2 antagonists of circling behaviour induced by dopamine agonists in rats with unilateral 6-hydroxydopamine lesions.
  10. Differential perikaryal localization in rats of D1 and D2 dopamine receptors on striatal projection neuron types identified by retrograde labeling.
  11. Dopamine D1 receptors synergize with D2, but not D3 or D4, receptors in the striatum without the involvement of action potentials.
  12. Dopamine receptor interactions in the brain. In:
  13. Dopamine supersensitivity and D1/D2 synergism are unrelated to changes in striatal receptor density.
  14. (1986). Effects of estrogen on the basal ganglia. Neurosci Biobehav Rev.
  15. (1989). Enhanced behavioral stereotypies elicited by intrastriatal injection D1 and D2 dopamine agonists in intact rats. Brain Res.
  16. (1999). Estrous cycle differences in cocaine-induced stereotypic and locomotor behaviors in Fischer rats. Behav Brain Res.
  17. (1989). Estrous cycle-dependent variation in amphetamine-induced behaviors and striatal dopamine release assessed with microdialysis. Behav Brain Res.
  18. Ethological resolution of behavioral topography and D2-like vs D1-like agonist responses in congenic D4 dopamine receptor “knockouts”: identification of D4:D1-like interactions.
  19. (1977). Evidence for dopamine receptors in the human brain mediating sedation and sleep. Life Sci.
  20. Galanin GAL-R1 receptor null mutant mice display increased anxiety-like behavior specific to the elevated plus-maze.
  21. Gonadectomy and sex differences in the behavioral responses to amphetamine and apomorphine of rats.
  22. (1985). Hyperactivity induced by stimulation of separate dopamine D-1 and D-2 receptors in rats with bilateral 6-OHDA lesions. Life Sci.
  23. (1988). Is stimulation of both D1 and D2 receptors necessary for the expression of dopamine-mediated behaviors? Pharmacol Biochem Behav.
  24. Lesions of the nigrostriatal dopamine projection increase the inhibitory effects of D1 and D2 dopamine agonists on caudate-putamen neurons and relieve D2 receptors from the necessity of D1 receptor stimulation.
  25. (1992). Molecular biology of dopamine receptors. Trends Pharmacol Sci.
  26. Obligatory D-1/D-2 receptor interaction in the generation of dopamine agonist related behaviors.
  27. (2008). Ontogeny and dopaminergic regulation in brain of ras homolog enriched in striatum (Rhes). Brain Res.
  28. (2003). Personality traits and striatal dopamine synthesis capacity in healthy subjects.
  29. (2011). Rhes and AGS1/Dexras1 affect signaling by dopamine D1 receptors through adenylyl cyclase. J Neurosci Res.
  30. Rhes is involved in striatal function.
  31. Rhes, the Ras homolog enriched in striatum, is reduced under conditions of dopamine supersensitivity.
  32. (1999). Rhes: A striatal-specific Ras homolog related to Dexras1. J Neurosci Res.
  33. (1990). Selemon LD. New frontiers in basal ganglia research. Introduction. Trends Neurosci.
  34. Sex differences in cocainestimulated motor behavior: disparate effects of gonadectomy.
  35. (1983). Sex differences in dopaminergic and cholinergic activity and function in the nigro-striatal system of the rat. Psychoneuroen docrinology.
  36. Sexually dimorphic link between dopamine D2 receptor gene and neuroticism-anxiety.
  37. (1993). Striatal Fos expression is indicative of dopamine D1/D2 synergism and receptor supersensitivity.
  38. (1988). Susceptibility to sensitization. II. The influence of gonadal hormones on enduring changes in brain monoamines and behavior produced by the repeated administration of D- amphetamine or restraint stress. Behav Brain Res.
  39. The comparative efficacy of buspirone and diazepam in the treatment of anxiety.
  40. The GTP-binding protein Rhes modulates dopamine signalling in striatal medium spiny neurons.
  41. The monomeric G proteins AGS1 and Rhes selectively influence Galphai-dependent signaling to modulate N-type (CaV2.2) calcium channels.
  42. The Ras homolog Rhes affects dopamine D1 and D2 receptor-mediated behavior in mice.
  43. The relation between dopamine D2 receptor density and personality: preliminary evidence from the NEO personality inventory-revised.

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