Role of the neurokinin-1 receptors in ejaculation in anesthetized rats.
BACKGROUND
Several lines of evidence indicate a role for substance P in the control of ejaculation, although its mode of action needs to be clarified.


OBJECTIVE
The effects and sites of action of a selective antagonist for the substance P-preferred receptor (neurokinin-1 receptor subtype; NK1) were investigated in a pharmacological model of ejaculation.


METHODS
Ejaculation was induced in anesthetized rats by intracerebroventricular (i.c.v.) delivery of the dopamine D3 receptor preferring agonist 7-hydroxy-2-(di-N-propylamino)tetralin (7-OH-DPAT). The effects of the selective NK1 antagonist RP67580 on 7-OH-DPAT-induced ejaculation were measured following intraperitoneal (i.p.), i.c.v., or intrathecal (i.t.) (third lumbar spinal segment; L3) administration.


METHODS
Intraseminal vesicle pressure (SVP) and electromyogram of the bulbospongiosus muscle (BS) were recorded as physiological markers of emission and expulsion phases of ejaculation, respectively.


RESULTS
Upon i.p., i.c.v., or i.t. administration, RP67580 significantly reduced the occurrence of ejaculation elicited by 7-OH-DPAT. A mild decrease in the occurrence of SVP and BS responses was observed in rats treated ip with RP67580, whereas only SVP responses were moderately affected following i.c.v. or i.t. administration.


CONCLUSIONS
These results show the multilevel regulation of 7-OH-DPAT-induced ejaculation by NK1 receptors.
Clement
Pierre
P
Pelvipharm Laboratories, Orsay, France. p.clement@pelvipharm.com
Peeters
Magali
M
Bernabe
Jacques
J
Laurin
Miguel
M
Alexandre
Laurent
L
Giuliano
Francois
F
D000758:Anesthesia; D000818:Animals; D018491:Dopamine Agonists / Q000008:administration & dosage / Q000494:pharmacology; D004542:Ejaculation / Q000187:drug effects*; D004576:Electromyography; D054833:Isoindoles / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects; D010410:Penile Erection / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D050638:Receptors, Dopamine D4 / Q000187:drug effects; D013373:Substance P / Q000378:metabolism; D013764:Tetrahydronaphthalenes / Q000008:administration & dosage / Q000494:pharmacology
D018491:Dopamine Agonists; D054833:Isoindoles; D013764:Tetrahydronaphthalenes; C071693:7,7-diphenyl-2-(1-imino-2-(2-methoxyphenyl)ethyl)perhydroisoindol-4-one; D050638:Receptors, Dopamine D4; D013373:Substance P; C031349:7-hydroxy-2-N,N-dipropylaminotetralin