Involvement of dopamine neurons in the regulation of beta-adrenergic receptor sensitivity in rat prefrontal cortex.
The contribution of dopamine (DA) afferents to the regulation of beta-adrenergic receptor sensitivity (isoproterenol-stimulated adenylate cyclase activity) in the rat prefrontal cortex was investigated by comparing the effects of lesions affecting either both DA and noradrenaline (NA) or NA fibers alone. Bilateral 6-hydroxydopamine (6-OHDA) lesions made in the ventral tegmental area destroyed ascending DA and to a variable extent ascending NA fibers innervating the prefrontal cortex. Two opposite effects were observed depending on the extent of cortical NA denervation: (a) When NA denervation was complete (less than 4% of controls), a marked increase in the isoproterenol-sensitive adenylate cyclase activity (+78%) was found. The amplitude of this denervation supersensitivity was similar to that occurring following complete and selective destruction of NA innervation induced by bilateral 6-OHDA injections made into the pedunculus cerebellaris superior. (b) When 6-OHDA injections into the ventral tegmental area led to a partial destruction of cortical NA afferents (10-40% of control values), a hyposensitivity of the isoproterenol-induced adenylate cyclase activity (-30%) was observed. This effect contrasted with the moderate supersensitivity seen in rats with partial, but selective, destruction of NA innervation (pedunculus cerebellaris superior lesions). The hyposensitivity of beta-adrenergic receptors obtained in rats with partial lesions of cortical NA fibers, but devoid of cortical DA innervation, suggests that DA neurons may regulate, under certain conditions, the denervation supersensitivity of beta-adrenergic receptors.
Hervé
D
D
INSERM U114, Chaire de Neuropharmacologie, Collège de France, Paris.
Trovero
F
F
Blanc
G
G
Vezina
P
P
Glowinski
J
J
Tassin
J P
JP
D000262:Adenylyl Cyclases / Q000378:metabolism; D000344:Afferent Pathways / Q000502:physiology; D000818:Animals; D002531:Cerebellum / Q000502:physiology; D003714:Denervation; D004298:Dopamine / Q000502:physiology*; D005625:Frontal Lobe / Q000201:enzymology / Q000378:metabolism*; D006892:Hydroxydopamines; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009412:Nerve Fibers / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D016627:Oxidopamine; D051381:Rats; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D013681:Tegmentum Mesencephali / Q000502:physiology
D006892:Hydroxydopamines; D011943:Receptors, Adrenergic, beta; D016627:Oxidopamine; D000262:Adenylyl Cyclases; D007545:Isoproterenol; D004298:Dopamine