Alpha2-adrenoceptor mediated co-release of dopamine and noradrenaline from noradrenergic neurons in the cerebral cortex.
Previous results suggest that extracellular dopamine (DA) in the rat cerebral cortex originates from dopaminergic and noradrenergic terminals. To further clarify this issue, dialysate DA, dihydroxyphenylacetic acid (DOPAC) and noradrenaline (NA) were measured both in the medial prefrontal cortex (mPFC) and in the occipital cortex (OCC), with dense and scarce dopaminergic projections, respectively. Moreover, the effect of the alpha2-adrenoceptor antagonist RS 79948 and the D2-receptor antagonist haloperidol on extracellular DA, DOPAC and NA was investigated. Extracellular DA and DOPAC concentrations in the OCC were 43% and 9%, respectively, those in the mPFC. Haloperidol (0.1 mg/kg i.p.) increased DA and DOPAC (by 35% and 150%, respectively) in the mPFC, but was ineffective in the OCC. In contrast, RS 79948 (1.5 mg/kg i.p.) increased NA, DA and DOPAC, both in the mPFC (by approximately 50%, 60% and 130%, respectively) and the OCC (by approximately 50%, 80% and 200%, respectively). Locally perfused, the DA transporter blocker GBR 12909 (10 micro m) was ineffective in either cortex, whereas desipramine (DMI, 100 micro m) markedly increased extracellular NA and DA in both cortices. The weak haloperidol effect on DA efflux was not enhanced after DA- and NA-transporter blockade, whereas after DMI, RS 79948 markedly increased extracellular NA, and especially DA and DOPAC in both cortices. The results support the hypothesis that most extracellular DA in the cortex is co-released with NA from noradrenergic terminals, such co-release being primarily controlled by alpha2-adrenoceptors.
Devoto
Paola
P
'B. B. Brodie' Department of Neuroscience Center of Excellence 'Neurobiology of Addiction', University of Cagliari, Italy. pdevoto@unica.it
Flore
Giovanna
G
Pira
Luigi
L
Longu
Giorgio
G
Gessa
Gian Luigi
GL
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D058669:Adrenergic alpha-2 Receptor Antagonists; D000818:Animals; D002540:Cerebral Cortex / Q000166:cytology*; D004298:Dopamine / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000494:pharmacology; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D004347:Drug Interactions; D005110:Extracellular Space / Q000378:metabolism; D006220:Haloperidol / Q000494:pharmacology; D007213:Indomethacin / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D017551:Microdialysis / Q000379:methods; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism*; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism*; D013997:Time Factors
D058669:Adrenergic alpha-2 Receptor Antagonists; D018492:Dopamine Antagonists; D018765:Dopamine Uptake Inhibitors; D010879:Piperazines; D018341:Receptors, Adrenergic, alpha-2; D015102:3,4-Dihydroxyphenylacetic Acid; C034674:5-hydroxyindomethacin; C043425:vanoxerine; D006220:Haloperidol; D004298:Dopamine; D009638:Norepinephrine; D007213:Indomethacin