, Volume 122, Issue 1, pp 1–14 | Cite as

Behavioural consequences of maternal exposure to natural cannabinoids in rats

  • M. Navarro
  • P. Rubio


Cannabis sativa preparations (hashish, marijuana) are the most widely used illicit drugs during pregnancy in Western countries. The possible long-term consequences for the child of in utero exposure to cannabis derivatives are still poorly understood. Animal models of perinatal cannabinoid exposure provide a useful tool for examining the developmental effects of cannabinoids. Behavioral consequences of maternal exposure to either cannabis preparations or to its main psychoactive component, Δ9-tetrahydrocannabinol (THC) in rat models are reviewed in this paper. Maternal exposure to cannabinoids resulted in alteration in the pattern of ontogeny of spontaneous locomotor and exploratory behavior in the offspring. Adult animals exposed during gestational and lactational periods exhibited persistent alterations in the behavioral response to novelty, social interactions, sexual orientation and sexual behavior. They also showed a lack of habituation and reactivity to different illumination conditions. Adult offspring of both sexes also displayed a characteristic increase in spontaneous and water-induced grooming behavior. Some of the effects were dependent on the sex of the animals being studied, and the dose of cannabinoid administered to the mother during gestational and lactational periods. Maternal exposure to low doses of THC sensitized the adult offspring of both sexes to the reinforcing effects of morphine, as measured in a conditioned place preference paradigm. The existence of sexual dimorphisms on the developmental effects of cannabinoids, the role of sex steroids, glucocorticoids, and pituitary hormones, the possible participation of cortical projecting monoaminergic systems, and the mediation of the recently described cannabinoid receptors are also analyzed. The information obtained in animal studies is compared to the few data available on the long-term behavioral and cognitive effects on in utero exposure to cannabis in humans.

Key words

Rat Development Behavior Cannabis Delta-9-tetrahydrocannabinol Motor activity Place preference Grooming Corticosterone 


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  1. Abel EL (1980) Prenatal exposure to cannabis: a critical review of effects on growth, development and behavior. Behav Neural Biol 29:137–145Google Scholar
  2. Abel EL (1983) Marihuana, tobacco, alcohol and reproduction. CRC Press, Boca Ratón, FloridaGoogle Scholar
  3. Abel EL, Day N, Dintcheff BA, Ernst CAS (1979) Inhibition of postnatal maternal performance in rats treated with marihuana extract during pregnancy. Bull Psychon Soc 4:353–359Google Scholar
  4. Abel EL, Dintcheff BA, Day N (1980) Effects of marihuana on pregnant rats and their offspring. Psychopharmacology 71:71–77Google Scholar
  5. Abood ME, Martin BR (1992) Neurobiology of marijuana abuse. Trends Pharmacol Sci 13:201–205Google Scholar
  6. Adams EG, Gfroerer JC, Rouse BA (1989) Epidemiology of substance abuse including alcohol and cigarette smoking. Ann NY Acad Sci 562:123–132Google Scholar
  7. Albert M, Solomon J (1984). Effect of neonatal administration of delta-9-tetrahydrocannabinol and/or estradiol benzoate (EB) on reproductive development and function of the male rat. In: Agurell S, Dewey WL, Willette RE (eds) Academic Press, Orlando, The cannabinoids: chemical, pharmacologic and therapeutic aspects. pp 339–344Google Scholar
  8. Andreasson S, Allebeck P, Engström A, Rydberg V (1987) Cannabis and schizophrenia: A longitudinal study of swedish conscripts. Lancet ii:1483–1486Google Scholar
  9. Arenander AT, de Vellis J (1989) Development of the nervous system. In: Siegel G, Agranoff B, Albers RW, Molinoff P (eds) Basic neurochemistry. Raven Press, New York, pp 479–506Google Scholar
  10. Arnold P, Gorski RA (1984) Gonadal steroid induction of structural sex differences in the central nervous system. Annu Rev Neurosci 7:413–442Google Scholar
  11. Berger B, Verney C, Alvarez C, Vigny A, Helle KB (1985a) Postnatal ontogenesis of the dopaminergic innervation in the rat anterior cingulate cortex (area 24). Immunocytohchemical and catecholamine fluorescence histochemical analysis. Dev Brain Res 21:31–47Google Scholar
  12. Berger B, Verney C, Gaspar P, Febvret A (1985b) Transient expression of tyrosine hydroxylase immunoreactivity in some neurons of the rat neocortex during postnatal development. Dev Brain Res 23:141–144Google Scholar
  13. Berridge KC, Fentress JC (1987) Disruption of natural grooming chains after striatopallidal lesions. Psychobiology 15:336–342Google Scholar
  14. Beyer C, Feder HH (1987) Sex steroids and afferent input: their roles in brain sexual differentiation. Annu Rev Physiol 49:349–364Google Scholar
  15. Bonnin A, Fernández-Ruiz JJ, Martín M, Rodríguez de Fonseca FA, de Miguel R, Ramos JA (1992) Estrogenic modulation of Δ9-Tetrahydrocannabinol effects on the nigrostriatal dopaminergic activity in the female rat brain. Mol Cell Neurosci 3:325–325Google Scholar
  16. Bonnin A, Ramos JA, Rodríguez de Fonseca F, Cebeira M, Fernández-Ruiz JJ (1993) The acute effects of Δ9-tetrahydrocannabinol on the tuberoinfundibular dopaminergic activity, the anterior pituitary sensitivity to dopamine and the prolactin release vary as a function of the estrous cycle. Neuroendocrinology 58:280–286Google Scholar
  17. Bonnin A, de Miguel R, Rodríguez-Manzaneque JC, Fernández-Ruiz JJ, Santos A, Ramos JA (1994) Changes in tyrosine hydroxylase gene expression in mesencephalic catecholaminergic neurons of immature and adult male rats perinatally exposed to cannabinoids. Dev Brain Res 81:147–153Google Scholar
  18. Borgen LA, Davis WN, Pace HB (1973) Effects of prenatal Δ9-tetrahydrocannabinol on the development of rat offspring. Pharmacol Biochem Behav 1:203–206Google Scholar
  19. Brake SC, Hutchings DE, Morgan B, Lasalle E, Shi T (1987) Delta-9-Tetrahydrocannabinol during pregnancy in the rat: II. Effects on ontogeny of locomotor activity and nipple attachment in the offspring. Neurotoxicol Teratol 9:45–49Google Scholar
  20. Callaghan PM, Delagarza R, Cunnighan KA, Henry C, Kabbaj M, Simon H, LeMoal M, Maccari (1994) Prenatal stress increases the hypothalamo-pituitary-adrenal axis response in young and adult rats. J Neuroendocrinol 6:341–345Google Scholar
  21. Chen J, Paredes W, Li J, Smith D, Lowinson J, Gardner EL (1990a) Delta-9-tetrahydrocannabinol produces naloxone-blockable enhancement of presynaptic basal dopamine efflux in nucleus accumbens of conscious, freely-moving rats as measured by intracerebral microdialysis. Psychopharmacology 102:156–162Google Scholar
  22. Chen J, Paredes W, Lowinson JH, Gardner EL (1990b) Delta-9-Tetrahydrocannabinol enhances presynaptic dopamine efflux in medial prefrontal cortex. Eur J Pharmacol 190:259–262Google Scholar
  23. Chen JJ, Smith ER (1979) Effects of perinatal alcohol on sexual differentiation and open field behavior in rats. Horm Behav 13:219–231Google Scholar
  24. Cole BJ, Cador M, Stinus, Rivier C, Rivier J, Vale W, Le Moal M, Koob GF (1990) Critical role of the hypothalamic pituitary adrenal axis in amphetamine-induced sensitization of behavior. Life Sci 47:1715–1720Google Scholar
  25. Conti LH, Musty RE (1984) The effects of delta-9-THC injections to the nucleus accumbens on the locomotor activity of rats. In: Agurell S, Dewey WL, Willette RE (eds). The cannabinoids: chemical, pharmacologic and therapeutic aspects. Academic Press, Orlando, pp 649–655Google Scholar
  26. Dalterio SL (1986) Cannabinoid exposure: effects on development. Neurobehav Toxicol Teratol 8:345–352Google Scholar
  27. Dalterio S, Bartke A (1979) Perinatal exposure to cannabinoids alters male reproductive function in mice. Science 205:1420–1422Google Scholar
  28. Dalterio S, Steger RW, Bartke A. (1984a) Maternal or paternal exposure to cannabinoids affects central neurotransmitter levels and reproductive function in male offspring. In: Agurell S, Dewey WL, Willette RE (eds). The cannabinoids: chemical, pharmacologic and therapeutic aspects. Academic Press, Orlando, pp 649–655Google Scholar
  29. Dalterio S, Steger RW, Mayfield D, Bartke A (1984b) Early cannabinoid exposure influences neuroendocrine and reproductive functions in male mice. I. Prenatal exposure. Pharmacol Biochem Behav 20:107–113Google Scholar
  30. Dalterio S, Steger RW, Mayfield D, Bartke A (1984c) Early cannabinoid exposure influences neuroendocrine and reproductive functions in male mice. II. Postnatal exposure. Pharmacol Biochem Behav 20:115–121Google Scholar
  31. Day NL, Richardson GA, Goldschmidt L, Robles N, Taylor PM, Stoffer DS, Cornelius MD, Geva D (1994) Effect of prenatal marijuana exposure on the cognitive development of offspring at age three. Neurotoxicol Teratol 16:169–175Google Scholar
  32. Deroche V, Piazza PV, LeMoal M, Simon H (1994) Social isolation-induced enhancement of the psychomotor effects of morphine depends on corticosterone secretion. Brain Res 640:136–139Google Scholar
  33. Devane WA, Dysarz III FA, Johnson MR, Melvin LS, Howlett AC (1988) Determination and characterization of a cannabinoid receptor in rat brain. Mol Pharmacol 34:605–613Google Scholar
  34. Devane WA, Hanus L, Breuer A, Pertwee RG, Stevenson RG, Griffin G, Gibson D, Mandelbaum, LA, Etinger A, Mechoulam R (1992) Isolation and structure of a brain constituent that binds to the cannabinoid receptor. Science 258:1946–1949Google Scholar
  35. Dewey WL (1986) Cannabinoid pharmacology. Pharmacol Rev 38:151–178Google Scholar
  36. Dow-Edwards DL (1989) Long-term neurochemical and neurobehavioral consequences of cocaine use during pregnancy. Ann NY Acad Sci 562:280–289Google Scholar
  37. Eldridge JC, Landfield PW (1990) Cannabinoid interactions with glucocorticoid receptors in rat hippocampus. Brain Res 534:135–141Google Scholar
  38. Fernández-Ruiz JJ, Rodríguez de Fonseca F, Navarro M, Ramos JA (1992) Maternal cannabinoid exposure and brain development: changes in the ontogeny of dopaminergic neurons. In: Bartke A, Murphy LL, (eds) Neurobiology and neurophysiology of cannabinoids, biochemistry and physiology of substance abuse, vol. IV. CRC Press, Boca Raton, Fla., pp 119–164Google Scholar
  39. Field E, Tyrey L (1990) Delayed sexual maturation during prepubertal cannabinoid treatment: importance of the timing of treatment. J Pharmacol Exp Ther 254:171–175Google Scholar
  40. Fride E, Mechoulam R (1993) Pharmacological activity of the cannabinoid receptor agonist anandamide, a brain constituent. Eur J Pharmacol 231:447–454Google Scholar
  41. PA (1976) Short and long-term effects of prenatal cannabis inhalation upon rat offspring. Psychopharmacologia 50:285–290Google Scholar
  42. Fried PA (1980) Marihuana use by pregnant women: neurobehavioral effects in neonates. Drug Alcohol Depend 6:415–424Google Scholar
  43. Fried PA (1984) Prenatal and postnatal consequences of marijuana use during pregnancy. In: Yanai J (ed) Neurobehavioral teratology. Amsterdam, Elsevier, pp 275–285Google Scholar
  44. Fried PA (1989) Postnatal consequences of marijuana use in humans. In: Hutchings DE (ed) Prenatal abuse of licit and illicit drugs. Ann NY Acad Sci 562:123–132Google Scholar
  45. Fried PA (1994) The Ottawa prenatal prospective study (OPPS): methodological issues and findings. Proceedings of the International Cannabis Research Society Meeting, L'Esterel, Quebec, July 21–23, p 46Google Scholar
  46. Fried PA, Charlebois AT (1979) Cannabis administered during pregnancy: first- and second- generation effects in rats. Physiol Psychol 7:307–312Google Scholar
  47. Fried PA, Watkinson B (1988) 12- and 24-month neurobehavioral follow-up of children prenatally exposed to marijuana, cigarettes and alcohol. Neurotoxicol Teratol 10:305–313Google Scholar
  48. Fried PA, Watkinson B (1990) 36- and 48- month neurobehavioral follow-up of children prenatally exposed to marijuana, cigarettes and alcohol. J Dev Behav Pediatr 11:49–58Google Scholar
  49. Gaoni Y, Mechoulam R (1964) Isolation, structure and partial synthesis on an active constituent of hashish. J Am Chem Soc 86:1646–1654Google Scholar
  50. Gardner EL (1992) Cannabinoid interaction with brain reward systems — the neurobiological basis of cannabinoid abuse. In: Bartke A, Murphy LL (eds) Neurobiology and neurophysiology of cannabinoids, Biochemistry and physiology of substance abuse, vol. IV. CRC Press, Boca Raton, Fla, pp 275–336Google Scholar
  51. Gianutsos A, Abbatiello ER (1972) The effect of prenatalCannabis sativa on maze learning ability in the rat. Psychopharmacology 27:117–122Google Scholar
  52. Golub MS, Sassenrath EN, Chapman LF (1981) Regulation of visual attention in offspring of female monkeys treated chronically with Δ9-Tetrahydrocannabinol. Dev Psychobiol 14:507–513Google Scholar
  53. Gruen RJ, Deutch AY, Roth RH (1990) Perinatal diazepam exposure: alterations in exploratory behavior and mesolimbic dopamine turnover. Pharmacol Biochem Behav 36:169–175Google Scholar
  54. Hainline B, Waller GI (1989) Effect of maternal marijuana and cocaine use on fetal growth. N Engl J Med 32:979Google Scholar
  55. Hatch EE, Bracken MB (1986) Effect of marihuana use in pregnancy of fetal growth. Am J Epidemiol 124:986–993Google Scholar
  56. Hatoum NS, Davis WM, Elsohly MA, Turner CE (1981) Perinatal exposure to cannabichromene and delta-9-tetrahydrocannabinol: separate and combined effects on viability of pups and on male reproductive system at maturity. Toxicol Lett 8:141–143Google Scholar
  57. Herkenham M, Lynn AB, Little MD, Johnson MR, Melvin LS, de Costa BR, Rice KC (1990) Cannabinoid receptor localization in brain. Proc Natl Acad Sci (USA) 87:1932–1936Google Scholar
  58. Herkenham M, Lynn AB, de Costa BR, Richfield EK (1991) Neuronal localization of cannabinoid receptors in the basal ganglia of the rat. Brain Res 547:267–274Google Scholar
  59. Howlett AC, Champion-Dorow TM, McMahon IL, Westlake TM (1991) The cannabinoid receptor: biochemical and cellular properties in neuroblastoma cells. Pharmacol Biochem Behav 40:565–569Google Scholar
  60. Hughes RN, Beveridge IJ (1990) Sex- and age-dependent effects of prenatal exposure to caffeine on open-field behavior, emergency latency and adrenal weights in rats. Life Sci 47:2075–2080Google Scholar
  61. Hutchings DE, Morgan B, Brake SC, Shi T, Lasalle E (1987) Delta-9-THC during pregnancy in the rat I: differential effects on maternal nutrition, embriotoxicity and growth in the offspring. Neurotoxicol Teratol 9:39–43Google Scholar
  62. Hutchings DE, Gamagaris Z, Miller N, Fico TA (1989a) The effects of prenatal exposure to Δ9-THC on the rest-activity cycle of the preweanling rat. Neurotoxicol Teratol 11:353–356Google Scholar
  63. Hutchings DE, Martin BR, Gamagaris Z, Miller N, Fico T (1989b) Plasma concentrations of delta-9-tetrahydrocannabinol in dams ans fetuses following acute or multiple prenatal dosing in rats. Life Sci 44:697–701Google Scholar
  64. Jakubovic A, Hattori T, Mc Geer PL (1977) Radiactivity in suckled rats after giving14−C-tetrahydrocannabinol to the mother. Eur J Pharmacol 22:221–223Google Scholar
  65. Kawash GF, Yeung DL, Berg SD (1980) Effects of administration of cannabis resin during pregnancy on emotionality and learning in rat offspring. Percept Motor Skills 50:359–365Google Scholar
  66. Koob GF, Heinrichs SC, Merlo-Pich E, Menzaghi F, Baldwin H, Miczek H, Britton KT (1993) The role of corticotropin-releasing factor in behavioural response to stress. In De Souza EB, Nemeroff CB (eds) Corticotropin-releasing factor: basic and clinical studies of a neuropeptide pp 277–295Google Scholar
  67. Kuhn C, Ignar D, Windh R (1991) Endocrine function as a target of perinatal drug effects: methodological issues. In: Kilbey MM, Asghar K (eds) Methodological issues in controlled studies on effects of prenatal exposure to drug abuse. US Department of Health and Human Services National Institute on Drug Abuse, Rockville, Maryland Research Monograph 114, pp 206–232Google Scholar
  68. Kumar AM, Haney M, Becker T, Thompson ML, Kream RM, Miczek K (1990) Effect of early exposure to delta-9-tetrahydrocannabinol on the levels of opioid peptides, gonadotrophin-releasing hormone and sustance P in the adult male rat brain. Brain Res 525:78–83Google Scholar
  69. Kumar AM, Solomon J, Patel V, Kream RM, Brieze JM, Millard WJ (1986) Early exposure to delta-9-THC influences neuroendocrine and reproductive functions in female rats. Neuroendocrinology 44:260–264Google Scholar
  70. Landfield PW, Cadwallader LB, Vinsant S (1988) Quantitative changes in hippocampal structure following chronic exposure to Δ-9tetrahydrocannabinol: possible mediation by glucocorticoid systems. Brain Res 443:47–62Google Scholar
  71. Lauder JM, Krebs H (1984) Neurotransmitters in development as possible substrates for drugs of use and abuse. In: Yanai I (ed) Neurobehavioral teratology. Elsevier Science Publishers Amsterdam, pp 289–314Google Scholar
  72. Lichtensteiger W, Schlumpf M (1984) Prenatal neuropharmacology: implications for neuroendocrine development. In: Ellendorf F, Gluckman PD, Porvizi N (eds) Fetal neuroendocrinology. (perinatology Press, Ithaca, NY) pp 59–70Google Scholar
  73. Mailleux P, Vanderhaeghen JJ (1992) Localization of cannabinoid receptor in the human developing and adult basal ganglia. Higher levels in the striatonigral neurons. Neurosci Lett 148:173–176Google Scholar
  74. Mailleux P, Vanderhaeghen JJ (1994) Delta-9-tetrahydrocannabinol regulates substance P and enkephalin messenger RNAs levels in the caudate putamen. Eur J Pharmacol (Mol Pharmacol section) 267:R1-R3Google Scholar
  75. Matsuda LA, Lolait SJ, Brownstein MJ, Young AC, Bonner TI (1990) Structure of a cannabinoid receptor and functional expression of the cloned cDNA. Nature 346:561–564Google Scholar
  76. McEwen BS (1987a) Steroid hormones: effect on brain development and function. Horm Res 37:1–10Google Scholar
  77. McEwen BS (1987b) Steroid hormones and brain development: some guidelines for understanding actions of pseudohormones and other toxic agents. Environ Health Perspect 74:177–192Google Scholar
  78. McGivern RF, Clancy AN, Hill MA, Noble EP (1984) Prenatal alcohol exposure alters adult expression of sexually dimorphic behaviors in the rat. Science 224:896–898Google Scholar
  79. McLaughlin CR, Abood ME (1993) Developmental expression of cannabinoid receptor mRNA. Dev Brain Res 76:75–78Google Scholar
  80. Mechoulam R (1970) Marihuana chemistry. Science 168:1159–1163Google Scholar
  81. Mirmiran M, Swaab DF (1987) Influence of drugs on brain neurotransmission and behavioral stages during development. Dev Pharmacol Ther 10:377–384Google Scholar
  82. Mokler DA, Robinson SE, Johnson JH, Hong JS, Rosecrans JA (1987) Neonatal administration of Δ9-tetrahydrocannabinol alters the neurochemical response to stress in the adult Fischer-344 rat. Neurotoxicol Teratol 9:321–326Google Scholar
  83. Molina VA, Wagner JM, Spear LP (1994) The behavioral response to stress is altered in adult rats exposed perinatally to cocaine. Physiol Behav 55:941–945Google Scholar
  84. Molina-Holgado F, Molina-Holgado E, Leret ML, González MI, Reader TA (1993). Distribution of indoleamines and [3H]-paroxetine binding in rat brain regions following acute or perinatal delta-9-tetrahydrocannabinol treatments. Neurochem Res 18:1183–1191Google Scholar
  85. Murphy LL, Steger RW, Bartke A (1990) Psychoactive and non-psychoactive cannabinoids and their effects on reproductive neuroendocrine parameters. In: Watson RR (ed) Biochemistry and physiology of substance abuse, vol. 2. CRC Press, Boca Raton, Fla., pp 73–94Google Scholar
  86. Murphy LL, Rodríguez de Fonseca FA, Steger RW (1991) Δ9-Tetrahydrocannabinol antagonism of the anterior pituitary response to estradiol in immature female rats. Steroids 56:97–102Google Scholar
  87. Nahas GG (1984) Toxicology and pharmacology. In: Nahas GG (ed) Marihuana in science and medicine. Raven Press, New York, pp 102–247Google Scholar
  88. Navarro M, Fernandez-Ruiz JJ, de Miguel R, Hernandez ML, Cebeira M, Ramos JA (1993a) An acute dose of Δ9-tetrahydrocannabinol affects behavioral and neurochemical indices of mesolimbic dopaminergic activity. Behav Brain Res 57:37–46Google Scholar
  89. Navarro M, Fernandez-Ruiz JJ, de Miguel R, Hernandez ML, Cebeira M, Ramos JA (1993b) Motor disturbances induced by an acute dose of Δ9-tetrahydrocannabinol: possible involvement of nigrostriatal dopaminergic alterations. Pharmacol Biochem Behav 45:291–298Google Scholar
  90. Navarro M, Rodríguez de Fonseca F, Hernández ML, Ramos JA, Fernández-Ruiz JJ (1994a) Changes in the adult motor behavior following perinatal cannabinoid exposure in rats: involvement of nigrostriatal dopaminergic activity. Pharmacol Biochem Behav 47:47–58Google Scholar
  91. Navarro M, Rubio P, Rodríguez de Fonseca F (1994b) Sex-dimorphic psychomotor activation after perinatal exposure to (-)-Δ9-tetrahydrocannabinol. An ontogenic study in wistar rats. Psychopharmacology 116:414–422Google Scholar
  92. Navarro M, de Miguel R, Rodríguez de Fonseca F, Ramos JA, Fernández-Ruiz JJ (1995) Perinatal cannabinoid exposure modifies the adult expression of several limbic behaviors. Behav Brain Res (In evaluation)Google Scholar
  93. Peters DAV, Tanf S (1982) Sex-dependent biological changes following prenatal nicotine exposure in the rat. Pharmacol Biochem Behav 17:1077–1083Google Scholar
  94. Robins LN, Mills JL (eds) (1993) Effects of in utero exposure to street drugs. Am J Public Health 83 [Suppl] pp 9–31Google Scholar
  95. Robinson TE, Berridge KC (1993) The neural basis of drug craving: an incentive-sensitization theory of addiction. Brain Res Rev 18:247–291Google Scholar
  96. Rodríguez de Fonseca FA (1993) Efectos de la exposición perinatal a extracto crudo de hachis sobre el desarrollo de la neurotransmisión dopaminérgica. Ph.D. dissertation. edited by Servicio de Publicaciones, Universidad Complutense de MadridGoogle Scholar
  97. Rodríguez de Fonseca F, Cebeira M, Hernández ML, Ramos JA, Fernández-Ruiz JJ (1990) Changes in brain dopaminergic indices induced by perinatal exposure to cannabinoids in rats. Dev Brain Res 51:237–240Google Scholar
  98. Rodríguez de Fonseca F, Cebeira M, Fernández-Ruiz JJ, Navarro M, Ramos JA (1991a) Effects of pre- and perinatal exposure to hashish extracts on the ontogeny of brain dopaminergic neurons. Neuroscience 43:713–723Google Scholar
  99. Rodríguez de Fonseca FA, Fernández-Ruiz JJ, Eldridge JC, Steger RW, Bartke A, Murphy L (1991b) Effects of the exposure to delta-9-tetrahydrocannabinol on the adrenal medullary function: evidence of an acute effect and development of tolerance in chronic treatments. Pharmacol Biochem Behav 40:593–598Google Scholar
  100. Rodríguez de Fonseca F, Hernández ML, de Miguel R, Fernández-Ruiz JJ, Ramos JA (1992) Early changes in the development of dopaminergic neurotransmission after maternal exposure to cannabinoids. Pharmacol Biochem Behav 41:469–474Google Scholar
  101. Rodríguez de Fonseca FA, Cebeira M, Ramos JA, Martín M, Fernández-Ruiz JJ (1993a) Cannabinoid receptors in rat brain areas: sexual differences, fluctuations during estrous cycle and changes after gonadectomy and sex steroid replacement. Life Sci 54:159–170Google Scholar
  102. Rodríguez de Fonseca F, Ramos JA, Bonnin A, Fernández-Ruiz JJ (1993b) Presence of cannabinoid binding sites in the brain from early postnatal ages. Neuroreport 4:135–138Google Scholar
  103. Rodríguez de Fonseca FA, Gorriti MA, Fernández-Ruiz JJ, Palomo T, Ramos JA (1994a). Down-regulation of rat brain cannabinoid binding sites after chronic Δ9-Tetrahydrocannabinol treatment. Pharmacol Biochem Behav 47:33–40Google Scholar
  104. Rodríguez de Fonseca F, Martín Calderón JL, Mechoulam R, Navarro M (1994b) Repeated Stimulation of D-1 dopamine receptors enhances (−)-11-hydroxy-Δ8-tetrahydrocannabinol-dimethylheptyl-induced catalepsy in male rats. Neuroreport 5:761–765Google Scholar
  105. Stewarr T, Rajabi H (1994) Estradiol dervied from testosterone in prenatal life affects the development of catecholamine systems in the frontal cortex in the male rat. Brain Res 646:157–160Google Scholar
  106. Vardaris RM, Weisz DJ (1976). Chronic administration of Δ-9-tetrahydrocannabinol to pregnant rats: studies of pup behavior and placental transfer. Pharmacol Biochem Behav 4:249–254Google Scholar
  107. Walters DE, Carr LA (1986) Changes in brain catecholamine mechanisms following perinatal exposure to marihuana. Pharmacol Biochem Behav 25:763–778Google Scholar
  108. Walters DE, Carr LA (1988) Perinatal exposure to cannabinoids alters neurochemical development in the rat brain. Pharmacol Biochem Behav 29:213–216Google Scholar
  109. Weisz J, Brown BL, Ward IL (1982) Maternal stress decreases aromatase activity in brains of male and female rat fetuses. Neuroendocrinology 35:374–380Google Scholar
  110. Wenger T, Croix D, Tramu G (1988) The effect of chronic prepuberal administration of marihuana (delta-9-THC) on the onset of puberty and the postpuberal reproductive functions in female rats. Biol Reprod 39:540–545Google Scholar
  111. Wenger T, Croix D, Tramu G, Leonardelli J (1992) Effects of Δ9-tetrahydrocannabinol on pregnancy, puberty, and the neuroendocrine system. In: Bartke A, Murphy LL (eds) Neurobiology and neurophysiology of cannabinoids, biochemistry and physiology of substance abuse, vol. IV. CRC Press, Boca Raton, Fla., pp 539–560Google Scholar
  112. Zuckerman B (1991) Drug effects — a search for mechanisms In: Kilbey MM, Asghar K (eds) Methodological issues in controlled studies on effects of prenatal exposure to drug abuse. NIDA Research Monograph 114, pp 352–362Google Scholar
  113. Zuckerman B, Frank DA, Hingson R, Amaro H, Levenson SM, Kayne H, Parker S, Vinci R, Aboagye K, Fried LE, Cabral H, Timperi R, Bauchner H (1989) Effects of maternal marijuana and cocaine use on fetal growth. N Engl J Med 320:762–768Google Scholar

Copyright information

© Springer-Verlag 1995

Authors and Affiliations

  • M. Navarro
    • 1
  • P. Rubio
    • 1
  1. 1.Fernando Rodríguez de Fonseca Instituto Complutense de Drogodependencias, Departmento de Psicobiología, Facultad de PsicologíaUniversidad ComplutenseMadridSpain

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