Skip to main content
SpringerLink
Log in

Behavioural consequences of maternal exposure to natural cannabinoids in rats

  • Review
  • Published:
Psychopharmacology Aims and scope Submit manuscript

Abstract

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.

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

  • Abel EL (1980) Prenatal exposure to cannabis: a critical review of effects on growth, development and behavior. Behav Neural Biol 29:137–145

    Google Scholar 

  • Abel EL (1983) Marihuana, tobacco, alcohol and reproduction. CRC Press, Boca Ratón, Florida

    Google Scholar 

  • 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 4:353–359

    Google Scholar 

  • Abel EL, Dintcheff BA, Day N (1980) Effects of marihuana on pregnant rats and their offspring. Psychopharmacology 71:71–77

    Google Scholar 

  • Abood ME, Martin BR (1992) Neurobiology of marijuana abuse. Trends Pharmacol Sci 13:201–205

    Google Scholar 

  • Adams EG, Gfroerer JC, Rouse BA (1989) Epidemiology of substance abuse including alcohol and cigarette smoking. Ann NY Acad Sci 562:123–132

    Google Scholar 

  • 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 339–344

    Google Scholar 

  • Andreasson S, Allebeck P, Engström A, Rydberg V (1987) Cannabis and schizophrenia: A longitudinal study of swedish conscripts. Lancet ii:1483–1486

    Google Scholar 

  • 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 479–506

    Google Scholar 

  • Arnold P, Gorski RA (1984) Gonadal steroid induction of structural sex differences in the central nervous system. Annu Rev Neurosci 7:413–442

    Google Scholar 

  • 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 21:31–47

    Google Scholar 

  • 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 23:141–144

    Google Scholar 

  • Berridge KC, Fentress JC (1987) Disruption of natural grooming chains after striatopallidal lesions. Psychobiology 15:336–342

    Google Scholar 

  • Beyer C, Feder HH (1987) Sex steroids and afferent input: their roles in brain sexual differentiation. Annu Rev Physiol 49:349–364

    Google Scholar 

  • 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 3:325–325

    Google Scholar 

  • 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 58:280–286

    Google Scholar 

  • 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 81:147–153

    Google Scholar 

  • Borgen LA, Davis WN, Pace HB (1973) Effects of prenatal Δ9-tetrahydrocannabinol on the development of rat offspring. Pharmacol Biochem Behav 1:203–206

    Google Scholar 

  • 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 9:45–49

    Google Scholar 

  • 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 6:341–345

    Google Scholar 

  • 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 102:156–162

    Google Scholar 

  • Chen J, Paredes W, Lowinson JH, Gardner EL (1990b) Delta-9-Tetrahydrocannabinol enhances presynaptic dopamine efflux in medial prefrontal cortex. Eur J Pharmacol 190:259–262

    Google Scholar 

  • Chen JJ, Smith ER (1979) Effects of perinatal alcohol on sexual differentiation and open field behavior in rats. Horm Behav 13:219–231

    Google Scholar 

  • 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 47:1715–1720

    Google Scholar 

  • 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 649–655

    Google Scholar 

  • Dalterio SL (1986) Cannabinoid exposure: effects on development. Neurobehav Toxicol Teratol 8:345–352

    Google Scholar 

  • Dalterio S, Bartke A (1979) Perinatal exposure to cannabinoids alters male reproductive function in mice. Science 205:1420–1422

    Google Scholar 

  • 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 649–655

    Google Scholar 

  • 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 20:107–113

    Google Scholar 

  • 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 20:115–121

    Google Scholar 

  • 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 16:169–175

    Google Scholar 

  • 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 640:136–139

    Google Scholar 

  • Devane WA, Dysarz III FA, Johnson MR, Melvin LS, Howlett AC (1988) Determination and characterization of a cannabinoid receptor in rat brain. Mol Pharmacol 34:605–613

    Google Scholar 

  • 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 258:1946–1949

    Google Scholar 

  • Dewey WL (1986) Cannabinoid pharmacology. Pharmacol Rev 38:151–178

    Google Scholar 

  • Dow-Edwards DL (1989) Long-term neurochemical and neurobehavioral consequences of cocaine use during pregnancy. Ann NY Acad Sci 562:280–289

    Google Scholar 

  • Eldridge JC, Landfield PW (1990) Cannabinoid interactions with glucocorticoid receptors in rat hippocampus. Brain Res 534:135–141

    Google Scholar 

  • 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 119–164

    Google Scholar 

  • Field E, Tyrey L (1990) Delayed sexual maturation during prepubertal cannabinoid treatment: importance of the timing of treatment. J Pharmacol Exp Ther 254:171–175

    Google Scholar 

  • Fride E, Mechoulam R (1993) Pharmacological activity of the cannabinoid receptor agonist anandamide, a brain constituent. Eur J Pharmacol 231:447–454

    Google Scholar 

  • PA (1976) Short and long-term effects of prenatal cannabis inhalation upon rat offspring. Psychopharmacologia 50:285–290

    Google Scholar 

  • Fried PA (1980) Marihuana use by pregnant women: neurobehavioral effects in neonates. Drug Alcohol Depend 6:415–424

    Google Scholar 

  • Fried PA (1984) Prenatal and postnatal consequences of marijuana use during pregnancy. In: Yanai J (ed) Neurobehavioral teratology. Amsterdam, Elsevier, pp 275–285

    Google Scholar 

  • 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 562:123–132

    Google Scholar 

  • 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 46

  • Fried PA, Charlebois AT (1979) Cannabis administered during pregnancy: first- and second- generation effects in rats. Physiol Psychol 7:307–312

    Google Scholar 

  • Fried PA, Watkinson B (1988) 12- and 24-month neurobehavioral follow-up of children prenatally exposed to marijuana, cigarettes and alcohol. Neurotoxicol Teratol 10:305–313

    Google Scholar 

  • 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 11:49–58

    Google Scholar 

  • Gaoni Y, Mechoulam R (1964) Isolation, structure and partial synthesis on an active constituent of hashish. J Am Chem Soc 86:1646–1654

    Google Scholar 

  • 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 275–336

    Google Scholar 

  • Gianutsos A, Abbatiello ER (1972) The effect of prenatalCannabis sativa on maze learning ability in the rat. Psychopharmacology 27:117–122

    Google Scholar 

  • Golub MS, Sassenrath EN, Chapman LF (1981) Regulation of visual attention in offspring of female monkeys treated chronically with Δ9-Tetrahydrocannabinol. Dev Psychobiol 14:507–513

    Google Scholar 

  • Gruen RJ, Deutch AY, Roth RH (1990) Perinatal diazepam exposure: alterations in exploratory behavior and mesolimbic dopamine turnover. Pharmacol Biochem Behav 36:169–175

    Google Scholar 

  • Hainline B, Waller GI (1989) Effect of maternal marijuana and cocaine use on fetal growth. N Engl J Med 32:979

    Google Scholar 

  • Hatch EE, Bracken MB (1986) Effect of marihuana use in pregnancy of fetal growth. Am J Epidemiol 124:986–993

    Google Scholar 

  • 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 8:141–143

    Google Scholar 

  • 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) 87:1932–1936

    Google Scholar 

  • Herkenham M, Lynn AB, de Costa BR, Richfield EK (1991) Neuronal localization of cannabinoid receptors in the basal ganglia of the rat. Brain Res 547:267–274

    Google Scholar 

  • Howlett AC, Champion-Dorow TM, McMahon IL, Westlake TM (1991) The cannabinoid receptor: biochemical and cellular properties in neuroblastoma cells. Pharmacol Biochem Behav 40:565–569

    Google Scholar 

  • 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 47:2075–2080

    Google Scholar 

  • 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 9:39–43

    Google Scholar 

  • 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 11:353–356

    Google Scholar 

  • 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 44:697–701

    Google Scholar 

  • Jakubovic A, Hattori T, Mc Geer PL (1977) Radiactivity in suckled rats after giving14−C-tetrahydrocannabinol to the mother. Eur J Pharmacol 22:221–223

    Google Scholar 

  • 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 50:359–365

    Google Scholar 

  • 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 277–295

  • 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 206–232

    Google Scholar 

  • 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 525:78–83

    Google Scholar 

  • 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 44:260–264

    Google Scholar 

  • 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 443:47–62

    Google Scholar 

  • 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 289–314

    Google Scholar 

  • 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 59–70

    Google Scholar 

  • 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 148:173–176

    Google Scholar 

  • 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-R3

    Google Scholar 

  • Matsuda LA, Lolait SJ, Brownstein MJ, Young AC, Bonner TI (1990) Structure of a cannabinoid receptor and functional expression of the cloned cDNA. Nature 346:561–564

    Google Scholar 

  • McEwen BS (1987a) Steroid hormones: effect on brain development and function. Horm Res 37:1–10

    Google Scholar 

  • McEwen BS (1987b) Steroid hormones and brain development: some guidelines for understanding actions of pseudohormones and other toxic agents. Environ Health Perspect 74:177–192

    Google Scholar 

  • McGivern RF, Clancy AN, Hill MA, Noble EP (1984) Prenatal alcohol exposure alters adult expression of sexually dimorphic behaviors in the rat. Science 224:896–898

    Google Scholar 

  • McLaughlin CR, Abood ME (1993) Developmental expression of cannabinoid receptor mRNA. Dev Brain Res 76:75–78

    Google Scholar 

  • Mechoulam R (1970) Marihuana chemistry. Science 168:1159–1163

    Google Scholar 

  • Mirmiran M, Swaab DF (1987) Influence of drugs on brain neurotransmission and behavioral stages during development. Dev Pharmacol Ther 10:377–384

    Google Scholar 

  • 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 9:321–326

    Google Scholar 

  • Molina VA, Wagner JM, Spear LP (1994) The behavioral response to stress is altered in adult rats exposed perinatally to cocaine. Physiol Behav 55:941–945

    Google Scholar 

  • 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 18:1183–1191

    Google Scholar 

  • 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 73–94

    Google Scholar 

  • Murphy LL, Rodríguez de Fonseca FA, Steger RW (1991) Δ9-Tetrahydrocannabinol antagonism of the anterior pituitary response to estradiol in immature female rats. Steroids 56:97–102

    Google Scholar 

  • Nahas GG (1984) Toxicology and pharmacology. In: Nahas GG (ed) Marihuana in science and medicine. Raven Press, New York, pp 102–247

    Google Scholar 

  • 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 57:37–46

    Google Scholar 

  • 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 45:291–298

    Google Scholar 

  • 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 47:47–58

    Google Scholar 

  • 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 116:414–422

    Google Scholar 

  • 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)

  • Peters DAV, Tanf S (1982) Sex-dependent biological changes following prenatal nicotine exposure in the rat. Pharmacol Biochem Behav 17:1077–1083

    Google Scholar 

  • Robins LN, Mills JL (eds) (1993) Effects of in utero exposure to street drugs. Am J Public Health 83 [Suppl] pp 9–31

  • Robinson TE, Berridge KC (1993) The neural basis of drug craving: an incentive-sensitization theory of addiction. Brain Res Rev 18:247–291

    Google Scholar 

  • 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 Madrid

  • 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 51:237–240

    Google Scholar 

  • 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 43:713–723

    Google Scholar 

  • 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 40:593–598

    Google Scholar 

  • 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 41:469–474

    Google Scholar 

  • 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 54:159–170

    Google Scholar 

  • 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 4:135–138

    Google Scholar 

  • 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 47:33–40

    Google Scholar 

  • 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 5:761–765

    Google Scholar 

  • 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 646:157–160

    Google Scholar 

  • Vardaris RM, Weisz DJ (1976). Chronic administration of Δ-9-tetrahydrocannabinol to pregnant rats: studies of pup behavior and placental transfer. Pharmacol Biochem Behav 4:249–254

    Google Scholar 

  • Walters DE, Carr LA (1986) Changes in brain catecholamine mechanisms following perinatal exposure to marihuana. Pharmacol Biochem Behav 25:763–778

    Google Scholar 

  • Walters DE, Carr LA (1988) Perinatal exposure to cannabinoids alters neurochemical development in the rat brain. Pharmacol Biochem Behav 29:213–216

    Google Scholar 

  • Weisz J, Brown BL, Ward IL (1982) Maternal stress decreases aromatase activity in brains of male and female rat fetuses. Neuroendocrinology 35:374–380

    Google Scholar 

  • 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 39:540–545

    Google Scholar 

  • 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 539–560

    Google Scholar 

  • 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 352–362

  • 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 320:762–768

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Fernando Rodríguez de Fonseca Instituto Complutense de Drogodependencias, Departmento de Psicobiología, Facultad de Psicología, Universidad Complutense, 28223, Madrid, Spain

    M. Navarro & P. Rubio

Authors
  1. M. Navarro
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. P. Rubio
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Navarro, M., Rubio, P. Behavioural consequences of maternal exposure to natural cannabinoids in rats. Psychopharmacology 122, 1–14 (1995). https://doi.org/10.1007/BF02246436

Download citation

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02246436

Key words

Search

Navigation