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Dopamine release induced by atypical antipsychotics in prefrontal cortex requires 5-HT(1A) receptors but not 5-HT(2A) receptors.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Bortolozzi, Analía Masana, Mercè Díaz-Mataix, Llorenç Cortés, R. Gutiérrez Scorza, María Cecilia Gingrich, Jay A. Tóth, Miklós Artigas, Francesc Pardo I |
| Copyright Year | 2010 |
| Abstract | Atypical antipsychotic drugs (APDs) increase dopamine (DA) release in prefrontal cortex (PFC), an effect probably mediated by the direct or indirect activation of the 5-HT(1A) receptor (5-HT(1A)R). Given the very low in-vitro affinity of most APDs for 5-HT(1A)Rs and the large co-expression of 5-HT(1A)Rs and 5-HT(2A) receptors (5-HT(2A)Rs) in the PFC, this effect might result from the imbalance of 5-HT(1A)R and 5-HT(2A)R activation after blockade of these receptors by APDs, for which they show high affinity. Here we tested this hypothesis by examining the dependence of the APD-induced DA release in medial PFC (mPFC) on each receptor by using in-vivo microdialysis in wild-type (WT) and 5-HT(1A)R and 5-HT(2A)R knockout (KO) mice. Local APDs (clozapine, olanzapine, risperidone) administered by reverse dialysis induced a dose-dependent increase in mPFC DA output equally in WT and 5-HT(2A)R KO mice whereas the DA increase was absent in 5-HT(1A)R KO mice. To examine the relative contribution of both receptors to the clozapine-induced DA release in rat mPFC, we silenced G-protein-coupled receptors (GPCRs) in vivo with N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) while 5-HT(1A)Rs or 5-HT(2A)/2CRs in the mPFC were selectively protected with the respective antagonists WAY-100635 or ritanserin. The inactivation of GPCRs while preserving ∼70% of 5-HT(2A)/(2C)Rs prevented the clozapine-induced DA rise in mPFC. In contrast, clozapine increased DA in mPFC of EEDQ-treated rats whose 5-HT(1A)Rs were protected (∼50% of control rats). These results indicate that (1) 5-HT(1A)Rs are necessary for the APDs-induced elevation in cortical DA transmission, and (2) this effect does not require 5-HT(2A)R blockade by APDs. |
| Starting Page | 550 |
| Ending Page | 550 |
| Page Count | 1 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://ijnp.oxfordjournals.org/content/ijnp/13/10/1299.full.pdf |
| Alternate Webpage(s) | http://digital.csic.es/bitstream/10261/76930/3/Dopamine%20release%20induced.pdf |
| PubMed reference number | 20158933v1 |
| Alternate Webpage(s) | https://doi.org/10.1017/S146114571000009X |
| DOI | 10.1017/s146114571000009x |
| Journal | The international journal of neuropsychopharmacology |
| Volume Number | 13 |
| Issue Number | 10 |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Antipsychotic Agents CFP gene Clozapine Dopamine EEDQ Knock-out Microdialysis Prefrontal Cortex Receptor, Serotonin, 5-HT1A Risperidone Ritanserin WAY 100635 olanzapine pamidronate |
| Content Type | Text |
| Resource Type | Article |
