title: Hyperfunctionality of serotonin-2C receptor-mediated inhibition of accumbal dopamine release in an animal model of depression is reversed by antidepressant treatment.
abstract: Dopamine release in the nucleus accumbens mediates motivation and reward, making it a likely candidate to be involved in anhedonia, one of the major symptoms of depression. In the current study, alterations in basal extracellular dopamine levels and 5HT2C receptor-mediated inhibition of accumbal dopamine release in Flinders Sensitive Line (FSL) rats, an animal model of depression, were investigated. We found that FSL rats have decreased extracellular dopamine levels in the nucleus accumbens and an increased inhibitory-like effect of 5HT2C receptors on accumbal dopamine release. However, neither basal 5HT levels nor the accumbal 5HT response to the local 5HT2C receptor antagonist (RS 102221) differed between Sprague-Dawley and FSL rats. Seven-day treatment with the nefazodone (a serotonin/noradrenaline reuptake inhibitor and 5HT2C antagonist) as well as 7-day and 14-day treatments with a tricyclic antidepressant desipramine increased extracellular dopamine levels in the nucleus accumbens of FSL rats. However, only 14-day treatment with desipramine or 7-day treatment with nefazodone, but not 7-day treatment with desipramine, decreased 5HT2C receptor-mediated inhibition of accumbal dopamine release. Based on a possible correlation between the onset of 5HT2C receptor-mediated inhibition and the behavioral effects of desipramine and nefazodone treatment that was described in our previous studies, we suggest that 5HT2C receptor activation may be important for the onset of the behavioral effects of antidepressant treatment.
authors.affiliation: Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel.
authors.forename: Eliyahu
authors.initials: E
authors.lastname: Dremencov
authors.forename: Michael E
authors.initials: ME
authors.lastname: Newman
authors.forename: Noa
authors.initials: N
authors.lastname: Kinor
authors.forename: Gitit
authors.initials: G
authors.lastname: Blatman-Jan
authors.forename: Cheryl J
authors.initials: CJ
authors.lastname: Schindler
authors.forename: David H
authors.initials: DH
authors.lastname: Overstreet
authors.forename: Gal
authors.initials: G
authors.lastname: Yadid
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology / Q000627:therapeutic use*; D003863:Depression / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D003891:Desipramine / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D008297:Male; D017551:Microdialysis / Q000379:methods; D023421:Models, Animal; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D010879:Piperazines; D051381:Rats; D017207:Rats, Sprague-Dawley; D044405:Receptor, Serotonin, 5-HT2C / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism; D058830:Serotonin 5-HT2 Receptor Antagonists; D013141:Spiro Compounds / Q000494:pharmacology; D013194:Staining and Labeling / Q000379:methods; D013449:Sulfonamides / Q000494:pharmacology; D013997:Time Factors; D014230:Triazoles / Q000494:pharmacology
chemical_list: C107821:8-(5-(5-amino-2,4-dimethoxyphenyl)-5-oxopentyl)-1,3,8-triazaspiro(4.5)decane-2,4-dione; D000929:Antidepressive Agents, Tricyclic; D010879:Piperazines; D044405:Receptor, Serotonin, 5-HT2C; D058830:Serotonin 5-HT2 Receptor Antagonists; D013141:Spiro Compounds; D013449:Sulfonamides; D014230:Triazoles; D012701:Serotonin; C051752:nefazodone; D003891:Desipramine; D004298:Dopamine