Effects of chronic selective serotonin reuptake inhibitors on 8-OH-DPAT-induced facilitation of ejaculation in rats: comparison of fluvoxamine and paroxetine.
BACKGROUND
Chronic treatment with selective serotonin reuptake inhibitors (SSRIs) can delay ejaculation in humans, but the extent of this effect differs between SSRIs. The involvement of 5-HT1A receptors is likely, since 5-HT1A receptor agonists accelerate ejaculation and chronic SSRI treatment is thought to desensitize 5-HT1A receptors.


OBJECTIVE
This study was conducted to examine the effects of chronic pretreatment with the SSRIs fluvoxamine and paroxetine on the facilitation of ejaculation induced by the 5-HT1A receptor agonist 8-OH-DPAT.


METHODS
Sexually experienced Wistar rats with normal ejaculatory behavior were treated for 22 days with vehicle, fluvoxamine (30 mg/kg/day), or paroxetine (10 or 20 mg/kg/day, p.o.). On day 22, rats received a challenge with saline or 8-OH-DPAT (0.4 mg/kg, s.c.). Sexual behavior was tested on days 1, 8, 15, and 22 of the SSRI-treatment.


RESULTS
Treatment with both doses of paroxetine, but not fluvoxamine, delayed ejaculation. 8-OH-DPAT strongly accelerated ejaculation under vehicle conditions. Pretreatment with paroxetine reduced the effects of 8-OH-DPAT on ejaculation in a dose-dependent manner and more strongly than fluvoxamine.


CONCLUSIONS
SSRIs affect 5-HT1A receptors involved in ejaculation. The degree to which this occurs, with paroxetine exerting a stronger effect than fluvoxamine, might determine the extent of SSRI-induced delayed ejaculation.
de Jong
Trynke R
TR
Department of Anatomy, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. t.dejong@pnf.umcn.nl
Pattij
Tommy
T
Veening
Jan G
JG
Waldinger
Marcel D
MD
Cools
Alexander R
AR
Olivier
Berend
B
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology*; D000818:Animals; D004542:Ejaculation / Q000187:drug effects*; D005260:Female; D016666:Fluvoxamine / Q000494:pharmacology*; D008297:Male; D017374:Paroxetine / Q000494:pharmacology*; 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; D016666:Fluvoxamine; D017374:Paroxetine; D017366:Serotonin Receptor Agonists; D017367:Selective Serotonin Reuptake Inhibitors
Neuroreport. 1999 Feb 25;10(3):493-5
10208577
Eur J Pharmacol. 1999 Aug 20;379(1):1-6
10499366
Life Sci. 2003 Feb 28;72(15):1665-82
12559389
Pharmacol Biochem Behav. 1991 Jul;39(3):605-12
1784589
Eur J Pharmacol. 1992 Jan 14;210(2):121-9
1534765
Br J Pharmacol. 1998 Dec;125(8):1733-43
9886765
Brain Res. 1999 Mar 13;821(2):414-25
10064829
Neuropharmacology. 2000;39(1):110-22
10665824
Eur J Pharmacol. 2000 Sep 1;403(1-2):55-65
10969144
Neuropharmacology. 1995 May;34(5):501-8
7566484
Psychopharmacology (Berl). 1995 Feb;117(3):358-63
7770611
Physiol Behav. 2004 Nov 15;83(2):309-17
15488547
J Chem Neuroanat. 2001 Jan;21(1):63-73
11173221
Eur J Pharmacol. 1997 Jul 2;330(1):1-9
9228408
Psychopharmacology (Berl). 2002 Dec;164(4):392-400
12457269
Psychopharmacology (Berl). 2002 Mar;160(3):283-9
11889497
Alcohol. 1999 Apr;17(3):195-201
10231167
Psychopharmacology (Berl). 1999 Jun;144(4):355-62
10435408
Behav Brain Res. 1998 May;92(2):111-8
9638953
Pharmacol Ther. 2000 Jan;85(1):11-28
10674711
Neuropharmacology. 1999 Aug;38(8):1083-152
10462127
Eur Neuropsychopharmacol. 1999 Jul;9 Suppl 3:S81-6
10523062
Life Sci. 1989;45(14 ):1263-70
2811596
Neuroreport. 1998 Aug 3;9(11):2535-8
9721928
Psychopharmacology (Berl). 1997 Feb;129(3):197-205
9084057
Psychopharmacology (Berl). 1998 Jun;137(4):374-82
9676898
Brain Res. 1999 Feb 27;820(1-2):55-62
10023030
J Neural Transm Gen Sect. 1991;85(2):95-107
1834089
Pharmacol Biochem Behav. 1981 Nov;15(5):785-92
6458826
Physiol Behav. 1997 Oct;62(4):881-91
9284512
J Pharmacol Exp Ther. 1999 Jan;288(1):98-106
9862759
Psychopharmacology (Berl). 1999 Feb;142(1):95-101
10102788
J Clin Psychopharmacol. 1999 Feb;19(1):67-85
9934946
J Pharmacol Exp Ther. 1997 Sep;282(3):1581-90
9316875
Eur J Pharmacol. 1992 Mar 3;212(2-3):241-6
1601066
Neurochem Res. 1997 Aug;22(8):1065-70
9239763
BJU Int. 2004 Jan;93(2):201-7
14690484
Pharmacol Biochem Behav. 1992 Jul;42(3):529-33
1409786
Naunyn Schmiedebergs Arch Pharmacol. 1995 Aug;352(2):141-8
7477436
Eur Neuropsychopharmacol. 2001 Feb;11(1):15-24
11226808
J Biol Chem. 1993 Nov 5;268(31):23422-6
8226867
Int Clin Psychopharmacol. 1998 Jul;13 Suppl 6:S27-33
9728672
Int J Impot Res. 2004 Aug;16(4):369-81
14961051