Effects of chronic paroxetine pretreatment on (+/-)-8-hydroxy-2-(di-n-propyl-amino)tetralin induced c-fos expression following sexual behavior.
Chronic treatment with the selective serotonin reuptake inhibitor paroxetine impairs the functioning of 5-HT(1A) receptors involved in ejaculation. This could underlie the development of delayed ejaculation often reported by men treated with paroxetine. The neurobiological substrate linking the effects of selective serotonin reuptake inhibitor-treatment and 5-HT(1A) receptor activation with ejaculation was investigated. Male Wistar rats that were pretreated with paroxetine (20 mg/kg/day p.o.) or vehicle for 22 days and had received an additional injection with the 5-HT(1A) receptor agonist 8-OH-DPAT ((+/-)-8-hydroxy-2-(di-n-propyl-amino)tetralin; 0.4 mg/kg s.c.) or saline on day 22, 30 min prior to a sexual behavior test, were perfused 1 h after the sexual behavior test. Brains were processed for Fos-, and oxytocin immunohistochemistry. The drug treatments markedly changed both sexual behavior and the pattern and number of Fos-immunoreactive cells in the brain. Chronic pretreatment with paroxetine caused delayed ejaculation. Acute injection with 8-OH-DPAT facilitated ejaculation in vehicle-pretreated rats, notably evident in a strongly reduced intromission frequency, whereas 8-OH-DPAT had no effects in paroxetine-pretreated rats. Chronic treatment with paroxetine reduced Fos-immunoreactivity in the locus coeruleus, and prevented the increase in Fos-immunoreactive neurons induced by 8-OH-DPAT in the oxytocinergic magnocellular part of the paraventricular nucleus as well as in the locus coeruleus. Since oxytocin and noradrenalin facilitate ejaculation, the alterations in Fos-IR in these areas could connect selective serotonin reuptake inhibitor treatment and 5-HT(1A) receptor activation to ejaculation. Chronic paroxetine treatment and 8-OH-DPAT changed c-fos expression in a number of other brain areas, indicating that Fos-immunohistochemistry is a useful tool to find locations where selective serotonin reuptake inhibitors and 8-OH-DPAT exert their effects.
de Jong
T R
TR
Department of Anatomy, Radboud University Nijmegen Medical Centre, The Netherlands. t.dejong@pnf.umcn.nl
Pattij
T
T
Veening
J G
JG
Dederen
P J W C
PJ
Waldinger
M D
MD
Cools
A R
AR
Olivier
B
B
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D004542:Ejaculation / Q000187:drug effects; D005260:Female; D007150:Immunohistochemistry; D008297:Male; D010121:Oxytocin / Q000187:drug effects / Q000378:metabolism; D017374:Paroxetine / Q000494:pharmacology*; D016760:Proto-Oncogene Proteins c-fos / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D012726:Sexual Behavior, Animal / Q000187:drug effects*
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D010121:Oxytocin; D017374:Paroxetine; D016760:Proto-Oncogene Proteins c-fos; D017366:Serotonin Receptor Agonists; D017367:Selective Serotonin Reuptake Inhibitors