Contribution of noradrenergic neurons to the regulation of dopaminergic (D1) receptor denervation supersensitivity in rat prefrontal cortex.
3,4-Dihydroxyphenylethylamine (DA, dopamine) levels in the rat prefrontal cortex were selectively decreased by 52%, leaving noradrenaline (NA) levels unaffected, 4 weeks following restricted bilateral electrolytic lesions of the ventral mesencephalic tegmentum (VMT). These lesions also induced a significant increase in DA-sensitive, but not isoproterenol-sensitive, adenylate cyclase activity in tissue homogenates (+38%). We had shown previously that chemical (6-hydroxydopamine, 6-OHDA) lesions of the VMT destroy both ascending DA and NA fibers but do not alter the D1-receptor density in the prefrontal cortex. In this study, electrolytic lesions of the VMT were combined with bilateral injections of 6-OHDA made laterally in the pedunculus cerebellaris superior to assess the role of NA fibers in the development of D1-receptor supersensitivity. This combined treatment produces a large decrease of cortical NA levels (-95%), an increase in beta-adrenergic-sensitive adenylate cyclase activity (+110%), and a decrease in DA levels (-60%), but does not alter D1-receptor density in the prefrontal cortex. These results indicate that the development of D1-receptor supersensitivity in the prefrontal cortex following electrolytic lesion of the VMT depends on the presence of an intact NA innervation.
Tassin
J P
JP
Studler
J M
JM
Hervé
D
D
Blanc
G
G
Glowinski
J
J
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D002540:Cerebral Cortex / Q000032:analysis / Q000502:physiology*; D003714:Denervation; D004298:Dopamine / Q000032:analysis; D006892:Hydroxydopamines; D008297:Male; D009474:Neurons / Q000502:physiology*; D009638:Norepinephrine / Q000032:analysis / Q000502:physiology*; D016627:Oxidopamine; D051381:Rats; D011919:Rats, Inbred Strains; D011941:Receptors, Adrenergic / Q000378:metabolism; D011954:Receptors, Dopamine / Q000502:physiology*; D013681:Tegmentum Mesencephali / Q000502:physiology
D006892:Hydroxydopamines; D011941:Receptors, Adrenergic; D011954:Receptors, Dopamine; D016627:Oxidopamine; D000262:Adenylyl Cyclases; D004298:Dopamine; D009638:Norepinephrine