Selective serotonin reuptake blockade increases extracellular dopamine in noradrenaline-rich isocortical but not prefrontal areas: dependence on serotonin-1A receptors and independence from noradrenergic innervation.
The present study investigated the effects of two serotonin (5-HT) uptake inhibitors, citalopram and paroxetine, and of a non-selective noradrenaline (NA) and 5-HT uptake blocker, imipramine, on extracellular NA and dopamine (DA) in the prefrontal cortex (PfCX), parietal cortex (ParCX) and occipital cortex (OccCX). Citalopram, the most selective 5-HT uptake blocker, increased dialysate DA in the OccCX and ParCX but not in the PfCX and this effect was prevented in the OccCX by WAY-100635, an antagonist of serotonin-1A (5-HT(1A)) receptors, but not by dorsal noradrenergic bundle (DNAB) lesions that reduced to unmeasurable levels basal dialysate NA but did not affect dialysate DA. Paroxetine, a less selective 5-HT uptake inhibitor than citalopram, at the dose of 5 mg/kg, increased DA in the OccCX but not in the PfCX; however, at doses of 10 mg/kg, which increase PfCX NA, paroxetine increased DA also in this area. Imipramine increased dialysate DA and NA both in the PfCX and in the OccCX and this effect was abolished by DNAB lesions and was reduced but not abolished by WAY-100635. Administration of doses of reboxetine and citalopram that do not increase DA release in the OccCX if given separately, markedly increased DA when combined. These results indicate that endogenous 5-HT, raised by selective blockade of the 5-HT carrier, can increase extracellular DA in the OccCX and in the ParCX by stimulating 5-HT(1A) receptors independently from the presence of NA terminals, although blockade of 5-HT and NA carrier can strongly interact to raise extracellular DA in this area. These observations are consistent with the existence of DA neurons separate from the NA ones contributing to extracellular DA even in NA-rich/DA poor isocortical areas.
Valentini
V
V
Department of Toxicology and Centre of Excellence 'Neurobiology of Addiction', University of Cagliari, Cagliari, Italy.
Cacciapaglia
F
F
Frau
R
R
Di Chiara
G
G
D000818:Animals; D004298:Dopamine / Q000378:metabolism*; D045604:Extracellular Fluid / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D009778:Occipital Lobe / Q000187:drug effects / Q000378:metabolism; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*
D004298:Dopamine; D009638:Norepinephrine; D044282:Receptor, Serotonin, 5-HT1A; D017367:Selective Serotonin Reuptake Inhibitors