Advertisement

Maternal or Paternal Exposure to Cannabinoids Affects Central Neurotransmitter Levels and Reproductive Function in Male Offspring

  • Susan L. Dalterio
  • Richard W. Steger
  • Andrzej Bartke
Chapter

Abstract

A single prenatal exposure to cannabinol or cannabidiol reduced brain norepinephrine and dopamine and hypothalamic NE concentrations, but increased brain levels of serotonin and its metabolite, 5-hydroxyindoleacetic acid. In addition, testicular testosterone concentrations and seminal vesicles weights were reduced in animals exposed to CBN. In contrast, seminal vesicles weights were increased in CBD-exposed males. Prenatal exposure to the major psychoactive component of marihuana, δ9-tetrahydrocannabinol on one of the last four days of gestation did not affect these parameters.

The F1 male offspring of male mice treated with CBN, CBD, or THC presented evidence of reduced fertility and testicular chromosomal abnormalities. In addition, two of the F1 male offspring of the THC-treated mice sired litters containing pups with severe congenital malformations.

These findings indicate that maternal or paternal exposure to cannabinoids can influence developmental and reproductive functions in offspring. Thus, cannabinoids appear to be both mutagenic and teratogenic in mice.

Keywords

Luteinizing Hormone Male Offspring Gonadal Steroid Adult Male Mouse Cholesterol Esterase 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
This is a preview of subscription content, log in to check access.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Bloch, E., Thysen, B., Morrill, G. A., Gardner, E. and Fujimoto, G. (1978) Effects of cannabinoids on reproduction and development. Vitam. Horm. 36, 203–258.PubMedCrossRefGoogle Scholar
  2. 2.
    Kolodny, R. C., Lessin, P., Toro, G., Masters, W. H. and Cohen, S. (1976) Depression of plasma testosterone with acute marihuana administration, in The Pharmacology of Marihuana ( Braude, M. C. and Szara, S., eds.), Raven, Press, New York, pp. 217–225.Google Scholar
  3. 3.
    Kolodny, R. C., Masters, W. H., Kolodner, R. M. and Toro, G. (1974) depression of plasma testosterone levels after chronic intensive marihuana use. N. Engl. J. Med. 290, 872–874.Google Scholar
  4. 4.
    Dalterio, S., Bartke, A., Roberson, C., Watson D. and Burstein, S. (1978) Direct and pituitary-mediated effects of 09-THC and cannabinol on the testis. Pharmacol. Biochem. Behay. 8, 673–678.CrossRefGoogle Scholar
  5. 5.
    Dalterio, S. (1980) Perinatal or adult exposure to cannabinoids alters male reproductive functions in mice. Pharmacol. Biochem. Behay. 12, 143–153.CrossRefGoogle Scholar
  6. 6.
    Dalterio, S. and Bartke, A. (1979) Perinatal exposure to cannabinoids alters male reproductive function in mice. Science 205, 1420–1422.PubMedCrossRefGoogle Scholar
  7. 7.
    Kramer, J. and Ben-David, M. (1978) Prolactin suppression by (-)-09-tetrahydrocannabinol (THC): involvement of serotonergic and dopaminergic pathways. Endocrinology 103 452–457.Google Scholar
  8. 8.
    Smith, C. G., Besch, N. F., Smith, R. G. and Besch, P. K. (1979) Effects of tetrahydrocannabinol on the hypothalamic-pituitary axis in the ovariectomized Rhesus monkey. Fertil. Steril. 31, 335–339.PubMedGoogle Scholar
  9. 9.
    Asch, R. H., Smith, C. G., Siler-Knodr, T. M. and Pauerstein, C. J. (1979) Effects of 09- tetrahydrocannabinol on gonadal steroidogenic activity in vivo. Fertil. Steril. 32, 576–582.PubMedGoogle Scholar
  10. 10.
    Fuxe, K. and Johnson, G. (1971) The effect of tetrahydrocannabinol on central monoamine neurons. Acta Pharm. Suec. 8, 695–701.Google Scholar
  11. 11.
    Ho, B. T., Taylor, D. V., Fritchie, G. E., Englert, G. E. and Mclsaac, W. M. (1973) Neuropharmacological study of A9-tetrahydrocannabinol in monkeys and mice. Brain Res. 38, 163–170.CrossRefGoogle Scholar
  12. 12.
    Han-is, L. S., Dewey, W. L. and Razdan, R. (1972) Cannabis: it’s chemistry, pharmacology, and toxicology, in Drug Addiction II (Martin, W. R., ed.) Handbook of Experimental Pharmacology, 45, 371–429.Google Scholar
  13. 13.
    Dewey, W. L., Poddar, M. K. and Johnson, K. M. (1979) The effects of cannabinoids on rat brain synaptosomes, in Marihuana, Biologic Effects ( Nahas, G. G. and Paton, W. D. M. eds.) Pergamon, Oxford, UK p. 343.Google Scholar
  14. 14.
    Bloom, A. S. (1982) Effect of 09-tetrahydrocannabinol on the synthesis of dopamine and norepinephrine in mouse brain synaptosomes. J. Pharmacol. Exp. Ther. 221, 97–103.PubMedGoogle Scholar
  15. 15.
    Dalterio, S., Badr, F., Bartke, A. and Mayfield, D. (1982) Cannabinoids in male mice: effects on fertility and spermatogenesis. Science 216, 315–316.PubMedCrossRefGoogle Scholar
  16. 16.
    Tyrey, L. (1980) Y-tetrahydrocannabinol: a potent inhibitor of episodic luteinizing hormone secretion. J. Pharmacol. Exp. Ther. 213, 300–308.Google Scholar
  17. 17.
    Jakubovic, A., McGeer, E. G. and McGeer, P. L. (1979) Effects of cannabinoids on testosterone and protein synthesis in rat testis Leydig cells in vitro. Molec. Cell. Endocrinol. 15, 41–50.PubMedCrossRefGoogle Scholar
  18. 18.
    Burstein, S., Levin, E. and Varanelli, C. (1973) Prostaglandins and cannabis II: inhibition of biosynthesis by the naturally occurring cannabinoids. Biochem. Pharmacol. 22, 2905–2910.PubMedCrossRefGoogle Scholar
  19. 19.
    Dalterio, S., Bartke, A., Harper, M. J. K., Huffman, R. and Sweeney, C. (1981) Effects of cannabinoids and female exposure on the pituitary-testicular axis in mice: possible involvement of prostaglandins. Biol. Reprod. 24, 315–322.Google Scholar
  20. 20.
    Husain, S. and Lame, M. W. (1981) Inhibitory effects of A9-tetrahydrocannabinol on glycolytic substrates in the rat testis. Pharmacology 23, 102–112.PubMedCrossRefGoogle Scholar
  21. 21.
    Shoupe, T. S., Hunter, S. A., Burstein, S. H. and Hubbard, C. D. (1980) Nature of the inhibition of cholesterol esterase by Al-tetrahydrocannabinol. Enzyme 25, 87–91.PubMedGoogle Scholar
  22. 22.
    Burstein, S., Hunter, S. A. and Shoupe, T. S. (1979) Site of inhibition of Leydig cell testosterone by Altetrahydrocannabinol. Molec. Pharmacol. 15, 663–640.Google Scholar
  23. 23.
    Dixit, V. P., Sharma, V. N. and Lohiya, N. K. (1974) The effect of chronically administered cannabis extract on the testicular function in mice. Eur. J. Pharmacol. 26, 111–114.PubMedCrossRefGoogle Scholar
  24. 24.
    Hembree, W. C., Nahas, G. G., Zeidenberg, P. and Dyrenfurth, I. (1976) Marihuana effects of the human testis. Clin. Res. 24, 272A.Google Scholar
  25. 25.
    Issidorides, M. R. (1979) Observations in chronic marihuana users: nuclear aberrations in blood and sperm and abnormal acrosomes in spermatozoa, in Marihuana, Biological Effects ( Nahas, G. G. and Paton, W. D. M. eds.) Pergamon, Oxford, UK, p 377.Google Scholar
  26. 26.
    Luthra, Y. K. (1979) Brain biochemical alterations in neonates of dams treated orally with A9-tetrahydrocannabinol during gestation lactation, in Marihuana, Biological Effects ( Nahas, G. G. and Paton, W. D. M., eds.) Pergamon, Press, Oxford, UK, p. 531.Google Scholar
  27. 27.
    Fried, P. A. (1976) Short and long term effects of prenatal cannabis inhalation upon rat offspring. Psychopharmacology 50, 285–291.PubMedCrossRefGoogle Scholar
  28. 28.
    Raduoco-Thomas, S., Magnan, F., Grove, R. N., Singh, P., Garcon, F. and Raduoco-Thomas, C. (1976) Effect of chronic administration of A9-THC on learning and memory in developing mice, in The Pharmacology of Marihuana ( Braude, M. C. and Szara, S, eds.) Raven, New York, p. 487.Google Scholar
  29. 29.
    Steger, R. W., DePaolo, L., Asch, R. H., and Silverman, A. V. (1982) Interactions of A9- tetrahydrocannabinol (THC) with hypothalamic neurotransmitters controlling luteinizing hormone and prolactin release. Neuroendocrinology (submitted).Google Scholar
  30. 30.
    Steger, R. W., Bartke, A. and Goldman, B. D. (1982) Alterations in neuroendocrine function during photoperiod-induced testicular atrophy and recrudiscence in the golden hamster. Biol. Reprod. 26, 437–444.PubMedCrossRefGoogle Scholar
  31. 31.
    Bapna, J., Neff, N. H. and Costa, E. (1971) A method for studying norepinephrine and serotonin metabolism in small regions of the brain: effect of ovariectomy on amine metabolism in anterior and posterior hypothalamus. Endocrinology 89, 1345–1349.PubMedCrossRefGoogle Scholar
  32. 32.
    Dalterio, S., Michael, S. D., Macmillan, B. T. and Bartke, A. (1981) Differential effects cannabinoid exposure and stress have on plasma prolactin, growth hormone and corticosterone levels in male mice. Life Sci. 28, 761–766.PubMedCrossRefGoogle Scholar
  33. 33.
    Dalterio, S., Bartke, A. and Sweeney, C. (1981) Interactive effects of ethanol and A9- tetrahydrocannabinolon endocrine functions in male mice. J. Androl. 2, 87–93.Google Scholar
  34. 34.
    Barraclough, C. A. and Wise, P. M. (1982) The role of catecholamines in the regulation of pituitary luteinizing hormone and follicle-stimulating hormone secretion. Endocrinol. Rev. 3, 91–119.CrossRefGoogle Scholar
  35. 35.
    Dalterio, S., Blum, K., Dellalo, L., Sweeney, C., Briggs, A. and Bartke, A. (1980) Perinatal exposure to A9THC in mice: altered enkephalin and norepinephrine sensitivity in vas deferens. Subs. Alcohol Actions/Misuse 1, 467–478.Google Scholar
  36. 36.
    Gessa, G. L. and Tagliamonte, A. (1975) Role of brain serotonin and dopamine in male sexual behavior, in Sexual Behavior: Pharmacology and Biochemistry Raven, New York, p. 117.Google Scholar
  37. 37.
    Wise, P. M., Rance, N. and Barraclough, C. A. (1981) Effects of estradiol and progesterone on catecholamine turnover in discrete hypothalamic regions on ovariectomized rats. Endocrinology 108 2186–2193.Google Scholar
  38. 38.
    Dalterio, S., Bartke, A., Michael, S. and Macmillan, B. (1980) Gonadal steroids influence the effects of A9tetrahydrocannabinol in male mice. Biol. Reprod. 22, 117A.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1999

Authors and Affiliations

  • Susan L. Dalterio
  • Richard W. Steger
  • Andrzej Bartke

There are no affiliations available

Personalised recommendations

Cite chapter

Buy options