Noradrenaline transporter blockers raise extracellular dopamine in medial prefrontal but not parietal and occipital cortex: differences with mianserin and clozapine.
This study compared the interaction between noradrenaline (NA) and dopamine (DA) mechanisms in the prefrontal (PFCX) and in the parietal (ParCX) and occipital (OccCX) cortex. The effect of reboxetine and desipramine, two NA transporter blockers, of mianserin, an antagonist of alpha2 and 5-HT2 receptors, and of clozapine, an atypical antipsychotic, on dialysate DA in the medial PFCX, ParCX and OccCX was studied. We also assessed the influence of a prior 6-hydroxydopamine (6-OHDA) lesion of the dorsal noradrenergic bundle (DNAB) on the effect of reboxetine and clozapine on dialysate DA in the PFCX and ParCX. Systemic administration of reboxetine and desipramine dose-dependently increased dialysate DA in the PFCX but not in the ParCX and OccCX. In contrast, mianserin and clozapine raised dialysate DA in the ParCX and OccCX to an even larger extent than in the PFCX. 6-OHDA lesions of DNAB abolished the increase of dialysate DA elicited by reboxetine in the PFCX and by clozapine both in the PFCX and in the ParCX. It is concluded that, although PFCX and ParCX/OccCX share the presence of a strong control of DA transmission by NA through alpha2 receptors, they differ in the extent to which DA is cleared from the extracellular compartment by uptake through the NA transporter. This process, although extensive in the PFCX, appears insignificant in the ParCX and OccCX, probably as a result of the higher ratio of NA to DA resulting in exclusion of DA from NA transporter.
Valentini
V
V
Department of Toxicology and Centre of Excellence 'Neurobiology of Addiction', University of Cagliari, Cagliari, Italy. gadichia@tiscali.it
Frau
R
R
Di Chiara
G
G
D000704:Analysis of Variance; D000818:Animals; D002540:Cerebral Cortex / Q000033:anatomy & histology / Q000187:drug effects* / Q000378:metabolism; D003024:Clozapine / Q000494:pharmacology*; D003891:Desipramine / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D004347:Drug Interactions; D005110:Extracellular Space / Q000187:drug effects; D008297:Male; D008803:Mianserin / Q000494:pharmacology*; D017551:Microdialysis; D009025:Morpholines / Q000494:pharmacology; D009434:Neural Pathways / Q000293:injuries; D050484:Norepinephrine Plasma Membrane Transport Proteins; D016627:Oxidopamine / Q000633:toxicity; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077593:Reboxetine; D012702:Serotonin Antagonists / Q000494:pharmacology*; D027981:Symporters / Q000037:antagonists & inhibitors*; D013997:Time Factors
D018765:Dopamine Uptake Inhibitors; D009025:Morpholines; D050484:Norepinephrine Plasma Membrane Transport Proteins; D010879:Piperazines; D012702:Serotonin Antagonists; C493226:Slc6a2 protein, rat; D027981:Symporters; D008803:Mianserin; D016627:Oxidopamine; C043425:vanoxerine; D000077593:Reboxetine; D003024:Clozapine; D003891:Desipramine; D004298:Dopamine