Time course of opioid and cannabinoid gene transcription alterations induced by repeated administration with fluoxetine in the rat brain.
This study examined the time course effects (8, 16 and 31 days) of fluoxetine administration (1 mg/kg, p.o./day) on serotonin transporter (5-HTT), opioid, tyrosine hydroxylase (TH) and cannabinoid CB1 receptor gene expressions in selected regions of the rat brain. Treatment with fluoxetine progressively decreased (35-55%) 5-HTT gene expression in dorsal raphe nucleus at 8, 16 and 31 days. The results revealed that fluoxetine administration decreased (30%) proenkephalin gene expression in nucleus accumbens shell (AcbS) and caudate-putamen (CPu) (31 days) but was without effect in nucleus accumbens core AcbC. A pronounced and time related decrease (25-65%) in prodynorphin gene expression was detected in AcbC, AcbS, CPu, hypothalamic supraoptic and paraventricular nuclei at all time points as well as in proopiomelanocortin gene expression (20-30%) in the arcuate nucleus (ARC) of the hypothalamus. On days 16 and 31, tyrosine hydroxylase gene expression in ventral tegmental area and substantia nigra and cannabinoid CB1 receptor gene expression in the CPu decreased (approximately 45-50% from vehicle). In conclusion, fluoxetine by inhibiting the reuptake of serotonin produced pronounced and time related alterations in genes involved in the regulation of emotional behaviour, suggesting that these neuroplastic changes may be involved, at least in part, in the clinical efficacy of this drug in neuropsychiatric disorders.
Oliva
José M
JM
Servicio de Psiquiatría y Unidad de Investigación, Hospital Universitario 12 de Octubre, Avda. de Córdoba s/n, 28041 Madrid, Spain.
Urigüen
Leyre
L
Pérez-Rial
Sandra
S
Manzanares
Jorge
J
D000818:Animals; D001345:Autoradiography; D001923:Brain Chemistry / Q000187:drug effects*; D004723:Endorphins / Q000096:biosynthesis* / Q000235:genetics*; D004745:Enkephalins / Q000096:biosynthesis / Q000235:genetics; D005473:Fluoxetine / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D007091:Image Processing, Computer-Assisted; D017403:In Situ Hybridization; D007700:Kinetics; D008297:Male; D008562:Membrane Glycoproteins / Q000187:drug effects / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000187:drug effects / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000187:drug effects / Q000378:metabolism; D011333:Pro-Opiomelanocortin / Q000096:biosynthesis / Q000235:genetics; D011498:Protein Precursors / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D043884:Receptor, Cannabinoid, CB1 / Q000096:biosynthesis* / Q000235:genetics*; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D004723:Endorphins; D004745:Enkephalins; D005473:Fluoxetine; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D011333:Pro-Opiomelanocortin; D011498:Protein Precursors; D012333:RNA, Messenger; D043884:Receptor, Cannabinoid, CB1; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; D014446:Tyrosine 3-Monooxygenase; C493232:Slc6a4 protein, rat; C029992:proenkephalin