title: Lack of D2 receptor mediated regulation of dopamine synthesis in A11 diencephalospinal neurons in male and female mice.
abstract: Dopamine (DA) neurons comprising the A11 diencephalospinal system represent the major source of DA innervation to the spinal cord. These neurons project axons throughout the rostrocaudal extent of the spinal cord, terminating predominantly in the dorsal horn. Loss of DA-mediated sensorimotor function in the lumbar segment of spinal cord is implicated in the etiology of Restless Legs Syndrome (RLS), which is more prevalent in females as compared with males. The purpose of the present study was to compare the density (DA concentrations) and catabolic activity (3,4-dihydroxyphenylacetic acid; DOPAC) of A11 DA neurons innervating the lumbar spinal cord of male and female C57/BL6 mice, and to determine if there is a sexual difference in the regulation of these neurons by D2 autoreceptor-mediated mechanisms. DA concentrations in the lumbar spinal cord were higher in males, suggesting a greater A11 DA innervation as compared with females, whereas there was no sexual difference in the activity (DOPAC/DA ratio) of these DA neurons under basal conditions. Blockade of D2 receptors with raclopride caused a significant increase in the DOPAC/DA ratio in the striatum and nucleus accumbens in both males and females, but had no effect in the spinal cord. Blockade of neuronal impulse flow and DA release with gamma-butyrolactone (GBL) increased DA concentrations in the spinal cord, but this increase was not prevented by pretreatment with the D2 agonist quinelorane. These results are consistent with the conclusion that A11 diencephalospinal DA neurons in both males and females lack presynaptic synthesis modulating D2 autoreceptors.
authors.affiliation: Department of Physiology, Michigan State University, East Lansing, MI 48824, USA.
authors.forename: Samuel S
authors.initials: SS
authors.lastname: Pappas
authors.forename: Bahareh
authors.initials: B
authors.lastname: Behrouz
authors.forename: Kelly L
authors.initials: KL
authors.lastname: Janis
authors.forename: John L
authors.initials: JL
authors.lastname: Goudreau
authors.forename: Keith J
authors.initials: KJ
authors.lastname: Lookingland
mesh_terms: D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D015107:4-Butyrolactone / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D004027:Diencephalon / Q000166:cytology*; D004298:Dopamine / Q000378:metabolism*; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D004347:Drug Interactions; D004563:Electrochemistry / Q000379:methods; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D011804:Quinolines / Q000494:pharmacology; D020891:Raclopride / Q000494:pharmacology; D017448:Receptors, Dopamine D2 / Q000502:physiology*; D012727:Sex Characteristics; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism
chemical_list: D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D011804:Quinolines; D017448:Receptors, Dopamine D2; D015102:3,4-Dihydroxyphenylacetic Acid; D020891:Raclopride; D015107:4-Butyrolactone; D004298:Dopamine; C047726:quinelorane