Efectos de la exposición prenatal a cocaína en la conducta emocional en ratones

  1. María del Pilar Santacruz 1
  2. Rosario Josefa Marrero Quevedo 2
  3. Juan Manuel Bethencourt Pérez 2
  4. Miguel Angel Castellano Gil 2
  5. Wenceslao Peñate Castro 2
  1. 1 Universidad Católica de Colombia

    Universidad Católica de Colombia

    Bogotá, Colombia

    ROR https://ror.org/01scwqh06

  2. 2 Universidad de La Laguna

    Universidad de La Laguna

    San Cristobal de La Laguna, España

    ROR https://ror.org/01r9z8p25

Diversitas: perspectivas en psicología

ISSN: 1794-9998

Year of publication: 2016

Volume: 12

Issue: 2

Pages: 275-293

Type: Article


In order to study the effects of prenatal cocaine exposure (0, 25 or 50 mg/kg/day), on the emotional behavior of young and adult mice of both sexes, 27 CD1 pregnant female mice were assigned to one of three experimental conditions: a control group was given saline solution, a first experimental group that was given 25 mg/kg/day of cocaine and another experimental group with 50 mg/kg/day of cocaine, all between gestational days 8-21. Emotional behavior was evaluated in the offspring (both males and females) of the females at five and seven weeks of age, via the hole board followed by the plus maze with different rates of exploratory activity. Data were analyzed with MANOVAS and ANOVAS with and α of 0.05. Prenatal Cocaine Exposure (PCE) altered dose-related emotional behavior; subjects with PCE of 50 mg/kg/day exhibited more anxiety and fear, in contrast to the 25 mg/kg/day group that explored more and showed greater high-risk behaviors, which are features of impulsivity and hyperactivity. The effects found were maintained over time, so it is concluded that PCE permanently and significantly perturbed emotion.

Bibliographic References

  • Ackerman, J. P., Riggins, T. & Black, M. M. (2010). A review of the effects of prenatal cocaine exposure among school-aged children. Pediatrics, 125, 554-565. doi: 10.1542/peds.2009-0637.
  • Bailey, K. R. & Crawley, J. N. (2009). Anxiety-related behaviors in mice. In J. J. Buccafusco (ed.). Methods of behavior analysis in neuroscience, (2). Boca Raton (Florida): CRC Press. Retrieved from http://www.ncbi.nlm.nih.gov/books/NBK5221/
  • Brown, G. R. & N emes, C . ( 2008). T he e xploratory behaviour of rats in the hole-board apparatus: is head-dipping a valid measure of neophilia? Behavior Processes, 78, 442-448. doi:10.1016/j.beproc.2008.02.019.
  • Brunton, P. J. (2015). Programming the brain and behaviour by early life stress: A focus on neuroactive steroids. Journal of Neuroendocrinology. doi:10.1111/jne.12265. Retrieved from http://onlinelibrary.wiley.com/doi/10.1111/jne.12265/pdf
  • Butler, T. R., Ariwodola, O. J. & Weiner, J. L. (2014). The impact of social isolation on HPA axis function, anxiety-like behaviors and ethanol drinking. Frontiers in Integrative Neuroscience, 2, 1-11. doi:10.3389/fnint.2013.00102.
  • Crawley, J. N. (2009). Chaplin, T. M., Freiburger, M. B., Mayes, L. C. & Sinha, R. (2010). Prenatal cocaine exposure gender and adolescent stress response: A prospective longitudinal study. Neurotoxicology Teratology, 32, 595- 604. doi:10.1016/j.ntt.2010.08.007.
  • Chaplin, T. M, Visconti K. J., Molfese, P. J., Susman, E. J., Klein, L. C., Sinha, R. & Mayes, L. C. (2014). Prenatal cocaine exposure differentially affects stress responses in girls and boys: Associations with future substance use. Development and Psychopathology, 18, 1-8. doi:10.1017/S0954579414000716.
  • Chrousos, G. P. & K ino, T . ( 2009). G lucocorticoid signaling in the cell. Expanding clinical implications to complex human behavioral and somatic disorders glucocorticoids and mood. Annals of the New York Academy of Sciences, 1179, 153-166. doi:10.1111/j.1749- 6632.2009.04988.
  • Costa-Goes, T., Dias-Antunes,F. & Teixeira-Silva, F. (2009). Trait and state anxiety in animal models: Is there correlation? Neuroscience Letters, 450, 26-269. doi:10.1016/j.neulet.2008.11.037.
  • Crawley, J. N. (1985). Exploratory behavior models of anxiety in mice. Neuroscience and Biobehavioral Reviews, 9, 37-44. doi:10.1016/0149- 7634(85)90030-2.
  • Dow-Edwards, D., Iijima, M., Stephenson, S., Jackson, A. & Weedon, J. (2014). The effects of prenatal cocaine, post-weaning housing and sex on conditioned place preference in adolescent rats. Psychopharmacology, 231, 1543- 1555. doi: 10.1007/s00213-013-3418-9.
  • Eiden, R. D., Schuetze, P. & Coles, C. D. (2011). Maternal cocaine use and mother-infant interactions: direct and moderated associations. Neurotoxicology and Teratology, 33, 120-128. doi:10.1016/j.ntt.2010.08.005.
  • Eyler, F. D., Warner, T. D., Behnke, M., Hou, W., Wobie, K. & G arvan, C . W. ( 2009). E xecutive functioning at ages 5 and 7 years in children with prenatal cocaine exposure. Devopmental Neuroscience, 31, 121-136. doi:10.1159/000207500.
  • Finger, B., Schuetze, P. & Eiden, R. (2015). Behavior problems among cocaine-exposed children: Role of physiological regulation and parenting. Drug & Alcohol Dependence, 146, 278. doi:10.1016/j.ntt.2014.01.001.
  • Golbach, T. (2005). The effects of prenatal cocaine exposure on the mutual regulation of attention in mother-infant dyads. Georgia State University. ProQuest issertations and Theses, 106. Retrieved from http://scholarworks.gsu.edu/psych_diss/5
  • Hansen-Trench, L. S. & Barron, S. (2005). Effects of neonatal alcohol and/or cocaine exposure on stress in juvenile and adult female rats. Neurotoxicology and Teratology, 27, 55–63. doi:10.1016/j.ntt.2004.10.001.
  • Huber, J., Darling S., Park, K. & Soliman, K.F. (2001). Altered responsiveness to stress and NMDA following prenatal exposure to cocaine. Physiology & Behavior, 72, 181-188. doi:10.1016/s0031-9384(00)00410-8.
  • Hughes, R. N. (2007). Neotic preferences in laboratory rodents: issues, assessment and substrates. Neuroscience Biobehavior Review, 31, 441-464. doi:10.1016/j.neubiorev.2006.11.004.
  • Konsolaki, E. & Skaliora, I. (2015). Motor vs. cognitive elements of apparent “hyperlocomotion”: A conceptual and experimental clarification. Proceedings of the National Academy of Sciences, 112, E 3-E4. doi:10.1073/pnas.1413820112.
  • Korte, M. & de Boerd, S. (2003). A robust animal model of state anxiety: fear-potentiated behavior in the elevated plus-maze. European Journal of Pharmacology, 463, 163-75. doi:10.1016/S0014-2999 (03)01279-2.
  • Laarakker, M. C., Ohl, F. & Van Lith, H. A. (2008). Chromosomal assignment of quantitative trait loci influencing modified hole board behavior in laboratory mice using consomic strains, with special reference to anxiety-related behavior and mouse chromosome 19. Behavior Genetics, 38, 159-184. doi:10.1007/s10519-007-9188-6.
  • Lambert, B. L. & Bauer, C . R . ( 2012). Developmental and behavioral consequences of prenatal cocaine exposure: A review. Journal of Perinatology, 32, 819–828. doi:10.1038/jp.2012.90.
  • Lester, B. M. & Padbury, J. F. (2009). Third pathophysiology of prenatal cocaine exposure. Developmental Neuroscience, 31, 23-35. doi:10.1159/000207491.
  • Lewis, M. W. (2015). Cocaine-exposed toddler caregiver dyads during free play at 24 months. In Society for social work and research 19th annual conference: The social and behavioral importance of increased longevity. Sswr.
  • Li, Z., Coles, C. D., Lynch, M. E., Hamann, S., Peltier, S., LaConte, S. & Hu, X. (2009). Prenatal
  • cocaine exposure alters emotional arousal regulation and its effects on working memory. Neurotoxicology and Teratology, 31, 342-348. doi:10.1016/j.ntt.2009.08.005.
  • Linares, T. J., Singer, L. T., Kirchner, H. L., Short, E. J., Min, M. Y., Hussey, P. & Minnes, S. (2006). Mental health outcomes of cocaine exposed children at 6 years of age. Journal of Pediatric Psychology, 31, 85-97. doi:10.1093/jpepsy/jsj020.
  • Loredo-Abdala, A. Casas-Muñoz, A. y Monroy-Llaguno, D. A. (2014). La cocaína: sus efectos en la mujer embarazada y en el producto de la gestación. Revista de la Facultad de Medicina de la UNAM, 57, 5-8.
  • Lynch, W. J., Roth, M. E. & Carroll, M. E. (2002). Biological basis of sex differences in drug abuse: Preclinical and clinical studies. Psychopharmacology, 164, 121-137. doi: 10.1007/s00213-002-1183-2.
  • Magalhães, A., Summavielle, T., Melo, P., Tavares, M. A. & Sousa, L. D. (2005). Prenatal cocaine exposure: effects on locomotor activity in rat offspring. Environmental Toxicology and Pharmacology, 19, 767-773. doi:doi.org/10.1016/j.etap.2004.12.043.
  • Mechan, A. O., Moran, P. M., Elliott, M. J., Walf, F. Young, A. M., Joseph, M. H., Green, R. A. & Frye, D. (2007). A study of the effect of a single neurotoxic dose of 3, 4-methylene dioxymethamphetamine (MDMA; “ecstasy”) on the subsequent long-term behaviour of rats in the plus maze and open field. Psychopharmacology, 159, 167-75. doi:10.1007/s002130100900.
  • Mechan, A. O., Moran, P. M., Elliott, M. J., Young, A. M., Joseph, M. H. & Green, R. A. (2002). A comparison between dark agouti and sprague- dawley rats in their behaviour on the elevated plus maze, open-field apparatus and activity meters, and their response to diazepam. Psychopharmacology, 159, 188-95. doi:10.1007/s002130100902.
  • Morrow, C. E., Accornero, V. H., Xue, L., Manjunath, S., Culbertson, J. L., Anthony, J. C. & Bandstra, E. S. (2009). Estimated risk of developing selected DSM-IV disorders among 5-year-old children with prenatal cocaine exposure. Journal of Child and Family Studies, 18(3), 356-364. doi:10.1007/s10826-008-9238-6.
  • Nnadi, C. U., Mimiko, O. A., McCurtis, H. L. & Cadet, J. L. (2005). Neuropsychiatric effects of cocaine use disorders. Journal of the National Medical Association, 97, 1504-1515.
  • Overstreet, D. H., Moy, S. S., Lubin, D. A., Gause, L. R., Lieberman, J. A. & Johns, J. M. (2000). Enduring effects of prenatal cocaine administration on emotional behavior in rats. Physiology & Behavior, 70, 149-156. doi:10.1016/s0031-9384(00)00245-6.
  • Peña-Oliver, Y. (2007). El enriquecimiento ambiental en ratas: efectos diferenciales en función del sexo. Tesis doctoral. España: Universidad de Barcelona. Departamento de Biología Celular. Recuperado de http://ddd.uab.cat/pub/tesis/2007/tdx-1031107-64745/ypo1de1.pdf
  • Salas-Ramírez, K. Y., Frankfurt, M., Alexander, A., Luine, V. N. & Friedman, E. (2010). Prenatal cocaine exposure increases anxiety, impairs Cognitive function and increases dendritic spine density in adult rats: influence of sex. Neuroscience, 169, 1287-1295. doi:10.1016/j.neuroscience.2010.04.067.
  • Salomons, A., Van Luijk, J., Reinders, N., Kirchhoff, S., Arndt, S. & Oh, F. (2010). Identifying emotional adaptation: behavioural habituation to novelty and immediate early gene expression in two inbred mouse strains. Genes, Brain and Behavior, 9, 1-10. doi:10.1111/j.1601-183X.2009.00527.x.
  • Simpson, J. (2011). The influence of housing, sex and strain on baseline and drug-induced behavioural and neurochemical parameters in the rat. Doctoral thesis. Galway, Ireland: School of Medicine, Department of Pharmacology and Therapeutics, National University of Ireland. Retrieved from http://aran.library.nuigalway.ie/xmlui/bitstream/handle/10379/3876/thesis%20resubmission_new%20appendix%20OCT%202013-1.pdf?sequence=5
  • Singer, L. T., Minnes, S., Short, E., Arendt, R., Farkas, K., Lewis, B., Klein, N., Russ, S. & Min, M. (2004). Cognitive outcomes of preschool children with prenatal cocaine exposure. The JAMA Network, 291, 2448-2456. doi:10.1001/jama.291.20.2448.
  • Sinha, R. (2008). Chronic stress, drug use and vulnerability to addiction. Annals of the New York Academy of Sciences, 1141, 105-130. doi:10.1196/annals.1441.030.
  • Sithisarn, T., Bada, H. S., Dai, H., Randall, D. C. & Legan, S. J. (2011). Effects of perinatal cocaine exposure on open field behavior and the response to corticotropin releasing hormone (CRH) in rat offspring. Brain Research, 1370, 136-144. doi:10.1016/j.brainres.2010.11.024.
  • Sobrian, S. K., Johnston, M., Wright, J., Kuhn, D. & Ameis, K . (2008). Prenatal nicotine or cocaine differentially alters nicotine-induced sensitization in aging offspring. Annals New York Academy of Sciences, 1139, 466-77. doi:10.1196/annals.1432.045.
  • Sobrian, S. K., Marr, L. & Ressman, K. (2003). Prenatal cocaine or nicotine exposure produces depression and anxiety in aging rats. Progress in Neuro-Psychopharmacology & Biological Psychiatry, 27, 501-18. doi:10.1016/S0278-5846(03)00042-3.
  • Thompson, B. L., Levitt, P. & Stanwood, G. (2005). Prenatal cocaine exposure specifically alters spontaneous alternation behavior. Behavioural Brain Research, 164, 107-116. doi:10.1016/j.bbr.2005.06.010.
  • UNODC. (2005). United Nations office on drugs and crime global; Illicit drug trends. Retrieved from https://www.unodc.org/unodc/en/data-and-analysis/WDR-2005.html
  • Walf, A. & Frye, Ch. (2007). The use of the elevated plus maze as an assay of anxiety-related behavior in rodents. Nature Protocols, 2, 322- 328. doi:10.1038/nprot.2007.44.