title: 6-Hydroxydopamine lesion in the ventral tegmental area fails to reduce extracellular dopamine in the cerebral cortex.
abstract: Dopamine and noradrenaline are both involved in modulation of superior cognitive functions that are mainly dependent on frontal cortex activity. Experimental evidence points to parallel variations in extracellular concentrations of catecholamines in the cerebral cortex, which leads us to hypothesize their corelease from noradrenergic neurons. This study aimed to verify this hypothesis, by means of cerebral microdialysis following destruction of dopaminergic innervation in rats. The unilateral injury of dopaminergic neurons, by 6-hydroxydopamine injection in the ventral tegmental area, dramatically reduced the immunoreactivity for dopamine transporter in the cerebral hemisphere ipsilateral to the lesion. Tissue dopamine content in the ipsilateral nucleus accumbens and medial prefrontal and parietal cortex was also profoundly decreased, whereas noradrenaline was only slightly affected. Despite the lower tissue content in the denervated side, the extracellular dopamine level was not changed in the cortex, although it was markedly decreased in the nucleus accumbens ipsilateral to the lesion. The effect of drugs selective for D(2)-dopaminergic (haloperidol) or alpha(2)-noradrenergic (RS 79948) receptors was verified. Haloperidol failed to modify extracellular dopamine in either cortex but increased it in the nucleus accumbens, such an increase being greatly reduced in the denervated side. On the other hand, RS 79948 increased extracellular dopamine and DOPAC in all areas tested, the increases being of the same degree in both intact and lesioned sides. The results strongly support the hypothesis that the majority of extracellular dopamine in the cortex, unlike that in the nucleus accumbens, originates from noradrenergic terminals.
authors.affiliation: "B.B. Brodie" Department of Neuroscience, University of Cagliari, Cagliari, Italy. pdevoto@unica.it
authors.forename: Paola
authors.initials: P
authors.lastname: Devoto
authors.forename: Giovanna
authors.initials: G
authors.lastname: Flore
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Saba
authors.forename: M Paola
authors.initials: MP
authors.lastname: Castelli
authors.forename: A Paola
authors.initials: AP
authors.lastname: Piras
authors.forename: William
authors.initials: W
authors.lastname: Luesu
authors.forename: M Cristina
authors.initials: MC
authors.lastname: Viaggi
authors.forename: M Grazia
authors.initials: MG
authors.lastname: Ennas
authors.forename: Gian Luigi
authors.initials: GL
authors.lastname: Gessa
mesh_terms: D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000494:pharmacology; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D004347:Drug Interactions; D045604:Extracellular Fluid / Q000378:metabolism; D006220:Haloperidol / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D008297:Male; D017551:Microdialysis / Q000379:methods; D009287:Naphthyridines / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism; D016627:Oxidopamine / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013565:Sympatholytics / Q000633:toxicity*; D017557:Ventral Tegmental Area / Q000293:injuries / Q000378:metabolism* / Q000503:physiopathology
chemical_list: D018492:Dopamine Antagonists; D050483:Dopamine Plasma Membrane Transport Proteins; D007546:Isoquinolines; D009287:Naphthyridines; C104875:RS 79948-197; D013565:Sympatholytics; D015102:3,4-Dihydroxyphenylacetic Acid; D016627:Oxidopamine; D006220:Haloperidol; D004298:Dopamine; D009638:Norepinephrine