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Activation of mu or delta opioid receptors in the lumbosacral spinal cord is essential for ejaculatory reflexes in male rats.

Kozyrev N, Coolen LM - PLoS ONE (2015)

Bottom Line: Intrathecal infusion of MOR or DOR antagonists effectively blocked ejaculatory reflexes induced by DPN stimulation.Both MOR and DOR agonists facilitated ejaculatory reflexes induced by subthreshold DPN stimulation in all animals.Activation of either MOR or DOR in LSt target areas is required for ejaculation, while MOR activation is sufficient to trigger ejaculation in the absence of sensory stimulation.

View Article: PubMed Central - PubMed

Affiliation: Department of Anatomy & Cell Biology, the University of Western Ontario, London, Ontario, Canada; Department of Physiology, University of Michigan, Ann Arbor, Michigan, United States of America.

ABSTRACT
Ejaculation is controlled by a spinal ejaculation generator located in the lumbosacral spinal cord, consisting in male rats of lumbar spinothalamic (LSt) cells and their inter-spinal projections to autonomic and motor centers. LSt cells co-express several neuropeptides, including gastrin releasing peptide (GRP) and enkephalin. We previously demonstrated in rats that GRP regulates ejaculation by acting within the lumbosacral spinal cord. In the present study, the hypothesis was tested that enkephalin controls ejaculation by acting on mu (MOR) or delta opioid receptors (DOR) in LSt target areas. Adult male rats were anesthetized and spinalized and received intrathecal infusions of vehicle, MOR antagonist CTOP (0.4 or 4 nmol), DOR antagonist (TIPP (0.4, 4 or 40 nmol), MOR agonist DAMGO (0.1 or 10 nmol), or DOR agonist deltorphin II (1.3 or 13 nmol). Ejaculatory reflexes were triggered by stimulation of the dorsal penile nerve (DPN) and seminal vesicle pressure and rhythmic contractions of the bulbocavernosus muscle were analyzed. Intrathecal infusion of MOR or DOR antagonists effectively blocked ejaculatory reflexes induced by DPN stimulation. Intrathecal infusion of DAMGO, but not deltorphin II triggered ejaculation in absence of DPN stimulation. Both MOR and DOR agonists facilitated ejaculatory reflexes induced by subthreshold DPN stimulation in all animals. Overall, these results support the hypothesis that enkephalin plays a critical role in the control of ejaculation in male rats. Activation of either MOR or DOR in LSt target areas is required for ejaculation, while MOR activation is sufficient to trigger ejaculation in the absence of sensory stimulation.

No MeSH data available.


Related in: MedlinePlus

Quantitative analyses of BCM events (A) bursts (B) and SVP increases (C) in response to 30 and 60 Hz DPN stimulation following infusions of saline in trial 1 (Saline-Controls 1–3; white bars) or one of three doses of TIPP (0.4, 4 or 40 nmol) in trial 2 (drug trial; filled bars).Trials 1 and 2 were conducted in the same animals, hence Saline-Control 1 are data for animals subsequently receiving TIPP 0.4 nmol in trial 2; Saline-Control 2 are data for animals receiving TIPP 4 nmol in trial 2; and Saline-Control 3 are data used for animals receiving TIPP 40 nmol in trial 2. Data are presented as Mean ± SEM. * denotes significant differences from trial 1 within the same treatment group, while # indicates significant differences between treatment groups within the same testing trial. BCM EMG traces of 90 seconds duration following 60 Hz DPN stimulation (arrow) after an intrathecal infusion of saline (D: control trial) and TIPP (E: same animal as in C).
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pone.0121130.g003: Quantitative analyses of BCM events (A) bursts (B) and SVP increases (C) in response to 30 and 60 Hz DPN stimulation following infusions of saline in trial 1 (Saline-Controls 1–3; white bars) or one of three doses of TIPP (0.4, 4 or 40 nmol) in trial 2 (drug trial; filled bars).Trials 1 and 2 were conducted in the same animals, hence Saline-Control 1 are data for animals subsequently receiving TIPP 0.4 nmol in trial 2; Saline-Control 2 are data for animals receiving TIPP 4 nmol in trial 2; and Saline-Control 3 are data used for animals receiving TIPP 40 nmol in trial 2. Data are presented as Mean ± SEM. * denotes significant differences from trial 1 within the same treatment group, while # indicates significant differences between treatment groups within the same testing trial. BCM EMG traces of 90 seconds duration following 60 Hz DPN stimulation (arrow) after an intrathecal infusion of saline (D: control trial) and TIPP (E: same animal as in C).

Mentions: There were main effects of testing trial on the numbers of BCM events for both 30 Hz (F(1,37) = 20.131; P < 0.001; Fig. 3A) and 60 Hz stimulation frequencies (F(1, 37) = 26.666; P < 0.001; Fig. 3A), main effect of drug dosage for 60 Hz (F2,37) = 6.18; P = 0.01) and significant interactions between testing trial and drug dosage for both 30 and 60 Hz (30 Hz: (F(2,37) = 5.861; P = 0.012; 60 Hz ((F(2,37) = 4.349; P = 0.031). Animals treated with the middle (4 nmol) and higher (40 nmol) but not the lower (0.4 nmol) dose of TIPP during trial 2 (drug trial) had significantly decreased BCM events in response to 30 Hz (P = 0.012: 4 nmol; P = <0.001: 40 nmol; Fig. 3A) and 60 Hz (60 Hz: P = 0.014, 4 nmol; P <0.001, 40 nmol; Fig. 3A) stimulation frequencies compared to saline treatment in trial 1 (control trial). In addition, there was an effect of dosage, as animals treated with the highest dose of TIPP (40 nmol) in the second trial (drug trial) displayed significantly fewer BCM events compared to those treated with the lower dose of TIPP (0.4 nmol) for both the 30 Hz (P = 0.004, 40 nmol; Fig. 3A) and 60 Hz (P < 0.001, 40 nmol; Fig. 3A) stimulation frequencies and compared to animals treated with the middle dose of TIPP (4 nmol) in response to the 60 Hz (P = 0.003, 4 nmol; Fig. 3A) stimulation (with a trend for the 30 Hz (P = 0.075, 4 nmol; Fig. 3A)).


Activation of mu or delta opioid receptors in the lumbosacral spinal cord is essential for ejaculatory reflexes in male rats.

Kozyrev N, Coolen LM - PLoS ONE (2015)

Quantitative analyses of BCM events (A) bursts (B) and SVP increases (C) in response to 30 and 60 Hz DPN stimulation following infusions of saline in trial 1 (Saline-Controls 1–3; white bars) or one of three doses of TIPP (0.4, 4 or 40 nmol) in trial 2 (drug trial; filled bars).Trials 1 and 2 were conducted in the same animals, hence Saline-Control 1 are data for animals subsequently receiving TIPP 0.4 nmol in trial 2; Saline-Control 2 are data for animals receiving TIPP 4 nmol in trial 2; and Saline-Control 3 are data used for animals receiving TIPP 40 nmol in trial 2. Data are presented as Mean ± SEM. * denotes significant differences from trial 1 within the same treatment group, while # indicates significant differences between treatment groups within the same testing trial. BCM EMG traces of 90 seconds duration following 60 Hz DPN stimulation (arrow) after an intrathecal infusion of saline (D: control trial) and TIPP (E: same animal as in C).
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Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4380469&req=5

pone.0121130.g003: Quantitative analyses of BCM events (A) bursts (B) and SVP increases (C) in response to 30 and 60 Hz DPN stimulation following infusions of saline in trial 1 (Saline-Controls 1–3; white bars) or one of three doses of TIPP (0.4, 4 or 40 nmol) in trial 2 (drug trial; filled bars).Trials 1 and 2 were conducted in the same animals, hence Saline-Control 1 are data for animals subsequently receiving TIPP 0.4 nmol in trial 2; Saline-Control 2 are data for animals receiving TIPP 4 nmol in trial 2; and Saline-Control 3 are data used for animals receiving TIPP 40 nmol in trial 2. Data are presented as Mean ± SEM. * denotes significant differences from trial 1 within the same treatment group, while # indicates significant differences between treatment groups within the same testing trial. BCM EMG traces of 90 seconds duration following 60 Hz DPN stimulation (arrow) after an intrathecal infusion of saline (D: control trial) and TIPP (E: same animal as in C).
Mentions: There were main effects of testing trial on the numbers of BCM events for both 30 Hz (F(1,37) = 20.131; P < 0.001; Fig. 3A) and 60 Hz stimulation frequencies (F(1, 37) = 26.666; P < 0.001; Fig. 3A), main effect of drug dosage for 60 Hz (F2,37) = 6.18; P = 0.01) and significant interactions between testing trial and drug dosage for both 30 and 60 Hz (30 Hz: (F(2,37) = 5.861; P = 0.012; 60 Hz ((F(2,37) = 4.349; P = 0.031). Animals treated with the middle (4 nmol) and higher (40 nmol) but not the lower (0.4 nmol) dose of TIPP during trial 2 (drug trial) had significantly decreased BCM events in response to 30 Hz (P = 0.012: 4 nmol; P = <0.001: 40 nmol; Fig. 3A) and 60 Hz (60 Hz: P = 0.014, 4 nmol; P <0.001, 40 nmol; Fig. 3A) stimulation frequencies compared to saline treatment in trial 1 (control trial). In addition, there was an effect of dosage, as animals treated with the highest dose of TIPP (40 nmol) in the second trial (drug trial) displayed significantly fewer BCM events compared to those treated with the lower dose of TIPP (0.4 nmol) for both the 30 Hz (P = 0.004, 40 nmol; Fig. 3A) and 60 Hz (P < 0.001, 40 nmol; Fig. 3A) stimulation frequencies and compared to animals treated with the middle dose of TIPP (4 nmol) in response to the 60 Hz (P = 0.003, 4 nmol; Fig. 3A) stimulation (with a trend for the 30 Hz (P = 0.075, 4 nmol; Fig. 3A)).

Bottom Line: Intrathecal infusion of MOR or DOR antagonists effectively blocked ejaculatory reflexes induced by DPN stimulation.Both MOR and DOR agonists facilitated ejaculatory reflexes induced by subthreshold DPN stimulation in all animals.Activation of either MOR or DOR in LSt target areas is required for ejaculation, while MOR activation is sufficient to trigger ejaculation in the absence of sensory stimulation.

View Article: PubMed Central - PubMed

Affiliation: Department of Anatomy & Cell Biology, the University of Western Ontario, London, Ontario, Canada; Department of Physiology, University of Michigan, Ann Arbor, Michigan, United States of America.

ABSTRACT
Ejaculation is controlled by a spinal ejaculation generator located in the lumbosacral spinal cord, consisting in male rats of lumbar spinothalamic (LSt) cells and their inter-spinal projections to autonomic and motor centers. LSt cells co-express several neuropeptides, including gastrin releasing peptide (GRP) and enkephalin. We previously demonstrated in rats that GRP regulates ejaculation by acting within the lumbosacral spinal cord. In the present study, the hypothesis was tested that enkephalin controls ejaculation by acting on mu (MOR) or delta opioid receptors (DOR) in LSt target areas. Adult male rats were anesthetized and spinalized and received intrathecal infusions of vehicle, MOR antagonist CTOP (0.4 or 4 nmol), DOR antagonist (TIPP (0.4, 4 or 40 nmol), MOR agonist DAMGO (0.1 or 10 nmol), or DOR agonist deltorphin II (1.3 or 13 nmol). Ejaculatory reflexes were triggered by stimulation of the dorsal penile nerve (DPN) and seminal vesicle pressure and rhythmic contractions of the bulbocavernosus muscle were analyzed. Intrathecal infusion of MOR or DOR antagonists effectively blocked ejaculatory reflexes induced by DPN stimulation. Intrathecal infusion of DAMGO, but not deltorphin II triggered ejaculation in absence of DPN stimulation. Both MOR and DOR agonists facilitated ejaculatory reflexes induced by subthreshold DPN stimulation in all animals. Overall, these results support the hypothesis that enkephalin plays a critical role in the control of ejaculation in male rats. Activation of either MOR or DOR in LSt target areas is required for ejaculation, while MOR activation is sufficient to trigger ejaculation in the absence of sensory stimulation.

No MeSH data available.


Related in: MedlinePlus