Skip to main content
SpringerLink
Log in

Inhibitory effect of opiates on male rat sexual behavior may be mediated by opiate receptors outside the central nervous system

  • Original Investigations
  • Published:
Psychopharmacology Aims and scope Submit manuscript

Abstract

The importance of opiate receptors outside the central nervous system for the inhibitory actions of morphine on male rat sexual behavior was evaluated. Morphine (10 mg/kg) produced an almost complete inhibition of sexual behavior. This inhibition was antagonized by naloxone at a dose of 1 mg/kg but not at a dose of 0.25 mg/kg. The quaternary opioid antagonist methylnaloxone effectively blocked the inhibitory actions of morphine at a dose of 20 mg/kg but not at a dose of 5 mg/kg. Since the affinity of methylnaloxone for opiate receptors is about 5% of that of naloxone, it may be concluded that both antagonists were about equally effective in inhibiting the effects of morphine. Furthermore, the opiate-like drug loperamide was found to inhibit sexual behavior. This drug acts mainly outside the central nervous system. Its effect was blocked by both naloxone and methylnaloxone, suggesting that opiate receptors are involved. It was also shown that methylnaloxone is unable to block the reinforcing effects of morphine in the conditioned place preference procedure. Because the reinforcing effects of opiates seem to be localized to the central nervous system, it may be proposed that methylnaloxone does not antagonize morphine's central effects. Moreover, loperamide had no effect in the place preference procedure, suggesting that this drug does not act at central opioid receptors. Taken together, these data show that peripheral opioid receptors are responsible for at least some of the inhibitory actions of morphine on male sexual behavior. After treatment with morphine + methylnaloxone, ejaculatory mechanisms were facilitated, reflected in a reduced number of preejaculatory intromissions and a shortened ejaculation latency. It thus appears that central opioid receptors facilitate sexual behavior while peripheral receptors participate in inhibitory mechanisms.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Ågmo A (1976) Cholinergic mechanisms and sexual behavior in the male rabbit. Psychopharmacology 51:43–45

    Google Scholar 

  • Ågmo A, Berenfeld R (1990) Reinforcing properties of ejaculation in the male rat: role of opioids and dopamine. Behav Neurosci 104:177–182

    Google Scholar 

  • Ågmo A, Gomez M (1991) Conditioned place preference produced by infusion of met-enkephalin into the medial preoptic area. Brain Res 550:343–346

    Google Scholar 

  • Ågmo A, Irazabal Y (1992) Enkephalinase inhibition facilitates sexual behavior in the male rat but does not produce conditioned place preference. Behav Neural Biol (in press)

  • Ågmo A, Paredes R (1988) Opioids and sexual behavior in the male rat. Pharmacol Biochem Behav 30:1021–1034

    Google Scholar 

  • Band LC, Hull EM (1990) Morphine and dynorphin (1–13) microinjected into the medial preoptic area and nucleus accumbens: effects on sexual behavior in male rats. Brain Res 524:77–84

    Google Scholar 

  • Bechara A, van der Kooy D (1985) Opposite motivational effects of endogenous opioids in brain and periphery. Nature 314:533–534

    Google Scholar 

  • Bechara A, Zito KA, van der Kooy (1987) Peripheral receptors mediate the aversive conditioning effects of morphine in the rat. Pharmacol Biochem Behav 28:219–225

    Google Scholar 

  • Bianchi C, Goi A (1977) On the antidiarrheal and analgesic properties of diphenoxylate, difenoxine and loperamide in mice and rats. Arzneimittelforschung 27:1040–1043

    Google Scholar 

  • Brown DR, Goldberg LI (1985) The use of quaternary narcotic antagonists in opiate research. Neuropharmacology 24:181–191

    Google Scholar 

  • Burleigh DE (1988) Opioid and non-opioid actions of loperamide on cholinergic nerve function in human isolated colon. Eur J Pharmacol 152:39–46

    Google Scholar 

  • Colpaert FC, Niemegeers CJE, Lal H, Janssen PA (1975) Investigations on drug produced and subjectively experienced discriminative stimuli. 2. Loperamide, an antidiarrheal devoid of narcotic cue producing actions. Life Sci 16:717–728

    Google Scholar 

  • Coulombe D (1984) Two-way ANOVA with and without repeated measurements, tests of simple main effects, and multiple comparisons for microcomputers. Behav Res Methods Instr Comp 16:397–398

    Google Scholar 

  • Damassa DA, Smith ER, Tennent B, Davidson JM (1977) The relationship between circulating testosterone levels and male sexual behavior in rats. Horm Behav 8:275–286

    Google Scholar 

  • Forsberg G, Bednar I, Eneroth P, Sodersten P (1987) Naloxone reverses post-ejaculatory inhibition of sexual behavior in female rats. J Endocrinal 113:429–434

    Google Scholar 

  • Forsberg G, Bednar I, Eneroth P, Sodersten P (1990) β-endorphin acts on the reproductive tract of female rats to suppress sexual receptivity. Neurosci Lett 115:92–96

    Google Scholar 

  • Giagnoni G, Casiraghi L, Senini R, Revel L, Parolaro D, Sala M, Gori E (1983) Loperamide: Evidence of interaction with μ and δ opioid receptors. Life Sci 33 [suppl 1]:315–318

    Google Scholar 

  • Greene WA, Foote RH (1978) Release rate of testosterone and estrogen from polydimethylsiloxane implants for extended periods in vivo compared with loss in vitro. Int J Fertil 23:128–132

    Google Scholar 

  • Harston CT, Spirtes MA, Dunlap WP, Coy DH (1980) Naloxone-reversible effects of d-ala2-met5-enkephalinamide induced behavioral activity in rats. Behav Neural Biol 30:1–19

    Google Scholar 

  • Hughes AM, Everitt BJ, Herbert J (1987) Selective effects of β-endorphin infused into the hypothalamus, preoptic area and bed nucleus of stria terminalis on the sexual and ingestive behaviour of male rats. Neuroscience 23:1063–1073

    Google Scholar 

  • Kalivas PW, Widerlow E, Stanley D, Breese G, Prange AJ Jr. (1983) Enkephalin action on the mesolimbic system: a dopamine-dependent and a dopamine-independent increase in locomotor activity. J Pharmacol Exp Ther 227:229–237

    Google Scholar 

  • Kumazawa T, Mizumura K, Sato J, Minagawa M (1989) Facilitatory effects of opioids on the discharges of visceral niciceptors. Brain Res 497:231–238

    Google Scholar 

  • LeMaire S, Magnan J, Regoli B (1978) Rat was deferens: a specific bioassay for endogenous opioid peptides. Br J Pharmacol 64:372–329

    Google Scholar 

  • Locke KW, Holtzman SG (1986) Behavioral effects of opioid peptides selective for mu or delta receptors. II. Locomotor activity in nondependent and morphine-dependent rats. J Pharmacol Exp Ther 238:997–1003

    Google Scholar 

  • Malmnäs CO (1977) Short-latency effects of testosterone on copulatory behavior in sexually experienced male rats. J Reprod Fertil 51:351–354

    Google Scholar 

  • Matuszweich L, Dornan WA (1990) Bilateral injections of morphiceptin into the medial preoptic nucleus produce a dramatic delay in the initation of sexual behavior in the male rat. Soc Neurosci Abstr 16:114.1

    Google Scholar 

  • McIntosh TK, Vallano ML, Barfield RJ (1980) Effects of morphine, β-endorphin and naloxone on catecholamine levels and sexual behavior in the male rat. Pharmacol Biochem Behav 13:435–441

    Google Scholar 

  • Meyerson BJ (1981) Comparison of the effects of β-endorphin and morphine on exploratory and socio-sexual behaviour in the male rat. Eur J Pharmacol 69:453–463

    Google Scholar 

  • Meyerson BJ, Terenius L (1977) β-endorphin and male sexual behaviour. Eur J Pharmacol 42:191–192

    Google Scholar 

  • Millan MJ, Herz A (1985) The endocrinology of opioids. Int Rev Neurobiol 26:1–84

    Google Scholar 

  • Misra AL, Pontani RB, Vadlamani NL, Mule SJ (1976) Physiological disposition and biotransformation of allyl-1′-3′-14C naloxone in the rat and some comparative observations on nalorphine. J Pharmacol Exp Ther 196:257–268

    Google Scholar 

  • Mitchell JB, Stewart J (1990) Facilitation of sexual behavior in the male rat associated with intra-VTA injections of opiates. Pharmacol Biochem Behav 35:643–650

    Google Scholar 

  • Mucha RF, Iversen SD (1984) Reinforcing properties of morphine and naloxone revealed by conditioned place preferences: a procedural examination. Psychopharmacology 82:241–247

    Google Scholar 

  • Mumford L, Kumar R (1979) Sexual behavior of morphine-dependent and abstinent male rats. Psychopharmacology 65:179–185

    Google Scholar 

  • Niemegeers CJE, Lenarts FM, Janssen PAJ (1974) Loperamide (R 18553), a novel type of antidiarrheal agent. Arzneimittelforschung 24:1636–1641

    Google Scholar 

  • Oka T, Hosoya E (1977) The different effect of humoral modulators on the morphine and central nervous system stimulant-induced hyperactivity of rats. Neuropharmacology 16:115–119

    Google Scholar 

  • Pellegrini Quarantotti B, Corda MG, Paglietti E, Biggio G, Gessa GL (1978) Inhibition of copulatory behavior byd-ala2-metenkephalinamide. Life Sci 23:673–678

    Google Scholar 

  • Pfaus JG, Gorzalka BB (1987) Opioids and sexual behavior. Neurosci Biobehav Rev 11:1–34

    Google Scholar 

  • Piercey MF, Ruwart MJ (1979) Naloxone inhibits the anti-diarrheal activity of loperamide. Br J Pharmacol 66:373–375

    Google Scholar 

  • Ruiz E, Ågmo A (1988) Enkephalin infusion into the medial preoptic area and sexual behavior in the male rat. 20th Ann Conf Reprod Behav, Omaha, Nebraska, p 83

  • Schnur P, Bravo F, Trujillo M, Rocha S (1983) Biphasic effects of morphine on locomotor activity in hamsters. Pharmacol Biochem Behav 18:357–361

    Google Scholar 

  • Tepperman FS, Hirst M, Smith P (1983) Brain and serum levels of naloxone following peripheral administration. Life Sci 33:1091–1096

    Google Scholar 

  • van der Kooy D, Nagy JI (1985) Hyperalgesia mediated by peripheral opiate receptors in the rat. Behav Brain Res 17:203–211

    Google Scholar 

  • van der Kooy D, Phillips AG (1977) Temporal analysis of naloxone attenuation of morphine-induced taste aversions. Pharmacol Biochem Behav 6:637–641

    Google Scholar 

  • Wise RA (1989) Opiate reward: Sites and substrates. Neurosci Biobehav Rev 13:129–133

    Google Scholar 

  • Wüster M, Herz A (1978) Opiate agonist action of antidiarrheal agents in vitro and in vivo — findings in support for selective action. Naunyn Schmiedeberg's Arch Pharmacol 301:187–194

    Google Scholar 

  • Zito KA, Bechara A, Greenwood C, van der Kooy D (1988) The dopamine innervation of the visceral cortex mediates the aversive effects of opiates. Pharmacol Biochem Behav 30:693–699

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Psychology, Universidad Anáhuac, Apartado Postal 10-844, 11000, Mexico City, D.F., Mexico

    Anders Ågmo, Jeanette Rojas & Pilar Vázquez

Authors
  1. Anders Ågmo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jeanette Rojas
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Pilar Vázquez
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

Supported by funds from the Universidad Anáhuac. Part of these data was presented at the 22nd Annual Conference on Reproductive Behavior, Atlanta, Georgia, June 8–11, 1990.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ågmo, A., Rojas, J. & Vázquez, P. Inhibitory effect of opiates on male rat sexual behavior may be mediated by opiate receptors outside the central nervous system. Psychopharmacology 107, 89–96 (1992). https://doi.org/10.1007/BF02244971

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02244971

Key words

Search

Navigation