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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 infusion, 5 Hz, 10 Hz, 30 Hz and 60 Hz DPN stimulation following intrathecal infusions of saline in trial 1 (Saline-Controls 1 and 2; white bars) or one of two doses of DAMGO (0.1 or 10 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 DAMGO 0.1 nmol in trial 2 and Saline-Control 2 are data for animals receiving DAMGO 10 nmol in trial 2. Note absence of white bars for infusions, 5, and 10 Hz, as these stimulation frequencies did not trigger BCM events, bursts, nor SVP increases in control conditions. 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. Representative BCM EMG traces (180 seconds duration) following an intrathecal infusion of saline (D: control trial) and DAMGO (E: 10 nmol: same animal as in D) in the absence of DPN stimulation. EMG and concurrent SVP traces (90 seconds duration) following 10 Hz DPN stimulation (arrow) after an intrathecal infusion of saline (F: control trial) and DAMGO (G: 0.1 nmol: same animal as in F).
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pone.0121130.g005: Quantitative analyses of BCM events (A) bursts (B) and SVP increases (C) in response to infusion, 5 Hz, 10 Hz, 30 Hz and 60 Hz DPN stimulation following intrathecal infusions of saline in trial 1 (Saline-Controls 1 and 2; white bars) or one of two doses of DAMGO (0.1 or 10 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 DAMGO 0.1 nmol in trial 2 and Saline-Control 2 are data for animals receiving DAMGO 10 nmol in trial 2. Note absence of white bars for infusions, 5, and 10 Hz, as these stimulation frequencies did not trigger BCM events, bursts, nor SVP increases in control conditions. 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. Representative BCM EMG traces (180 seconds duration) following an intrathecal infusion of saline (D: control trial) and DAMGO (E: 10 nmol: same animal as in D) in the absence of DPN stimulation. EMG and concurrent SVP traces (90 seconds duration) following 10 Hz DPN stimulation (arrow) after an intrathecal infusion of saline (F: control trial) and DAMGO (G: 0.1 nmol: same animal as in F).

Mentions: The effects of Mu opioid receptor agonist DAMGO on ejaculatory reflexes was examined in conditions in which such reflexes are not triggered in control conditions; i.e. sub threshold DPN stimulation (5–10 Hz), or in the absence of DPN stimulation (Infusion only). In addition, effects of DAMGO were tested on ejaculatory reflexes triggered by DPN stimulation parameters that reliably trigger such reflexes (30–60 Hz). The mu opioid receptor agonist DAMGO triggered BCM events, bursts and SVP increases in the absence of DPN stimulation (Infusion; Fig. 5). In addition, DAMGO dose-dependently facilitated BCM events, bursts and SVP increases induced by subthreshold levels of DPN stimulation (5–10 Hz; Fig. 5). For the numbers of BCM events, there were main effects of testing trial for all stimulation frequencies (Infusion (0 Hz: (F(1, 29) = 6.400; P = 0.025); 5 Hz: (F(1, 29) = 11.407; P = 0.005); 10 Hz:(F(1, 29) = 41.312; P < 0.001); 30 Hz (F(1, 29) = 42.443; P < 0.001); and 60 Hz (F(1, 29) = 73.256; P < 0.001); Fig. 5A). Moreover, there were effects of drug dosage (5 Hz: (F(1, 29) = 8.637; P = 0.012), 10 Hz:(F(1, 29) = 29.005; P < 0.001) and 30 Hz (F(1, 29) = 4.763; P = 0.048). DAMGO induced BCM events in the absence of DPN stimulation, but only following the higher dose (10 nmol) and in 100% of males (Infusion: P = 0.009 compared to saline in trial 1; p = 0.024 compared to lower dosage in trial 2; Fig. 5A). DAMGO treatment also induced BCM events following subthreshold DPN stimulation; but this effect was only observed with the lower dosage (0.1 nmol) and not the higher dose (10 nmol) (5–10 Hz: P< 0.001; compared to saline treatment in trial 1; 5–10 Hz: P < 0.001 compared to higher dosage in trial 2; Fig. 5A). In contrast, DAMGO reduced numbers of BCM events following 30 and 60 Hz DPN stimulation frequencies, which reliably triggered BCM activity following saline in trial 1 (Fig. 5A; 30Hz: P < 0.001, 10 nmol compared to saline in trial 1 and compared to lower dosage in trial 2; 60 Hz: P< 0.001, 10 nmol; P< 0.001, 0.1 nmol; compared to saline in trial 1).


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 infusion, 5 Hz, 10 Hz, 30 Hz and 60 Hz DPN stimulation following intrathecal infusions of saline in trial 1 (Saline-Controls 1 and 2; white bars) or one of two doses of DAMGO (0.1 or 10 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 DAMGO 0.1 nmol in trial 2 and Saline-Control 2 are data for animals receiving DAMGO 10 nmol in trial 2. Note absence of white bars for infusions, 5, and 10 Hz, as these stimulation frequencies did not trigger BCM events, bursts, nor SVP increases in control conditions. 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. Representative BCM EMG traces (180 seconds duration) following an intrathecal infusion of saline (D: control trial) and DAMGO (E: 10 nmol: same animal as in D) in the absence of DPN stimulation. EMG and concurrent SVP traces (90 seconds duration) following 10 Hz DPN stimulation (arrow) after an intrathecal infusion of saline (F: control trial) and DAMGO (G: 0.1 nmol: same animal as in F).
© Copyright Policy
Related In: Results  -  Collection

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

pone.0121130.g005: Quantitative analyses of BCM events (A) bursts (B) and SVP increases (C) in response to infusion, 5 Hz, 10 Hz, 30 Hz and 60 Hz DPN stimulation following intrathecal infusions of saline in trial 1 (Saline-Controls 1 and 2; white bars) or one of two doses of DAMGO (0.1 or 10 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 DAMGO 0.1 nmol in trial 2 and Saline-Control 2 are data for animals receiving DAMGO 10 nmol in trial 2. Note absence of white bars for infusions, 5, and 10 Hz, as these stimulation frequencies did not trigger BCM events, bursts, nor SVP increases in control conditions. 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. Representative BCM EMG traces (180 seconds duration) following an intrathecal infusion of saline (D: control trial) and DAMGO (E: 10 nmol: same animal as in D) in the absence of DPN stimulation. EMG and concurrent SVP traces (90 seconds duration) following 10 Hz DPN stimulation (arrow) after an intrathecal infusion of saline (F: control trial) and DAMGO (G: 0.1 nmol: same animal as in F).
Mentions: The effects of Mu opioid receptor agonist DAMGO on ejaculatory reflexes was examined in conditions in which such reflexes are not triggered in control conditions; i.e. sub threshold DPN stimulation (5–10 Hz), or in the absence of DPN stimulation (Infusion only). In addition, effects of DAMGO were tested on ejaculatory reflexes triggered by DPN stimulation parameters that reliably trigger such reflexes (30–60 Hz). The mu opioid receptor agonist DAMGO triggered BCM events, bursts and SVP increases in the absence of DPN stimulation (Infusion; Fig. 5). In addition, DAMGO dose-dependently facilitated BCM events, bursts and SVP increases induced by subthreshold levels of DPN stimulation (5–10 Hz; Fig. 5). For the numbers of BCM events, there were main effects of testing trial for all stimulation frequencies (Infusion (0 Hz: (F(1, 29) = 6.400; P = 0.025); 5 Hz: (F(1, 29) = 11.407; P = 0.005); 10 Hz:(F(1, 29) = 41.312; P < 0.001); 30 Hz (F(1, 29) = 42.443; P < 0.001); and 60 Hz (F(1, 29) = 73.256; P < 0.001); Fig. 5A). Moreover, there were effects of drug dosage (5 Hz: (F(1, 29) = 8.637; P = 0.012), 10 Hz:(F(1, 29) = 29.005; P < 0.001) and 30 Hz (F(1, 29) = 4.763; P = 0.048). DAMGO induced BCM events in the absence of DPN stimulation, but only following the higher dose (10 nmol) and in 100% of males (Infusion: P = 0.009 compared to saline in trial 1; p = 0.024 compared to lower dosage in trial 2; Fig. 5A). DAMGO treatment also induced BCM events following subthreshold DPN stimulation; but this effect was only observed with the lower dosage (0.1 nmol) and not the higher dose (10 nmol) (5–10 Hz: P< 0.001; compared to saline treatment in trial 1; 5–10 Hz: P < 0.001 compared to higher dosage in trial 2; Fig. 5A). In contrast, DAMGO reduced numbers of BCM events following 30 and 60 Hz DPN stimulation frequencies, which reliably triggered BCM activity following saline in trial 1 (Fig. 5A; 30Hz: P < 0.001, 10 nmol compared to saline in trial 1 and compared to lower dosage in trial 2; 60 Hz: P< 0.001, 10 nmol; P< 0.001, 0.1 nmol; compared to saline in trial 1).

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