Effects of prenatal cocaine and heroin exposure on neuronal dendrite morphogenesis and spatial recognition memory in mice

Cocaine and heroin are psychoactive substances frequently used by woman abusers of childbearing age. In this study, we used in utero electroporation labeling technique and novelty recognition models to evaluate the effects of prenatal exposure of mice to cocaine or heroin on the morphological development of cortical neurons and postnatal cognitive functions. Our results showed that prenatal cocaine exposure increased dendrite outgrowth, and prenatal heroin exposure decreased dendrite length and branch number in pyramidal neurons in the somatosensory cortex. Furthermore, although no effects of prenatal cocaine or heroin exposure on novel object recognition were observed, offspring prenatally exposed to cocaine exhibited no exploration preference for objects placed in novel locations, and mice prenatally exposed to heroin showed a reduced tendency of exploration for objects in novel locations. These data demonstrate that maternal cocaine or heroin administration during pregnancy causes morphological alterations in pyramidal neurons in the somatosensory cortex and suggest that prenatal administration of addictive substances may impair short-term spatial memory in adult offspring.

[1]  Richard J Smeyne,et al.  Regional differences in cortical dendrite morphology following in utero exposure to cocaine. , 2003, Brain research. Developmental brain research.

[2]  V. Luine,et al.  Prenatal cocaine exposure increases anxiety, impairs cognitive function and increases dendritic spine density in adult rats: influence of sex , 2010, Neuroscience.

[3]  J. Yanai,et al.  Disruption of the development of cholinergic-induced translocation/activation of PKC isoforms after prenatal heroin exposure , 2006, Brain Research Bulletin.

[4]  G. S. Wilson,et al.  Clinical Studies of Infants and Children Exposed Prenatally to Heroin , 1989, Annals of the New York Academy of Sciences.

[5]  M. Nader,et al.  Behavioral characterization of adult male and female rhesus monkeys exposed to cocaine throughout gestation , 2011, Psychopharmacology.

[6]  R. Roth,et al.  Prenatal cocaine exposure disrupts non-spatial, short-term memory in adolescent and adult male rats , 2002, Behavioural Brain Research.

[7]  Tetsuichiro Saito In vivo electroporation in the embryonic mouse central nervous system , 2006, Nature Protocols.

[8]  H. Bada,et al.  Effects of perinatal cocaine exposure on open field behavior and the response to corticotropin releasing hormone (CRH) in rat offspring , 2011, Brain Research.

[9]  I. Zagon,et al.  Opioid Receptor Blockade During Prenatal Life Modifies Postnatal Behavioral Development , 1997, Pharmacology Biochemistry and Behavior.

[10]  S. Glatt,et al.  A meta-analysis of animal studies on disruption of spatial navigation by prenatal cocaine exposure. , 2007, Neurotoxicology and teratology.

[11]  C D Holman,et al.  The relationship between maternal use of heroin and methadone and infant birth weight. , 1997, Addiction.

[12]  C. Vorhees,et al.  Effects of prenatal cocaine on Morris and Barnes maze tests of spatial learning and memory in the offspring of C57BL/6J mice. , 2000, Neurotoxicology and teratology.

[13]  P. Levitt,et al.  Nonuniform alteration of dendritic development in the cerebral cortex following prenatal cocaine exposure. , 1996, Cerebral cortex.

[14]  P. Levitt,et al.  Prenatal exposure to drugs: effects on brain development and implications for policy and education , 2009, Nature Reviews Neuroscience.

[15]  Joseph Yanai,et al.  Functional changes after prenatal opiate exposure related to opiate receptors' regulated alterations in cholinergic innervation. , 2003, The international journal of neuropsychopharmacology.

[16]  J. Shumsky,et al.  Prenatal cocaine exposure produces consistent developmental alterations in dopamine-rich regions of the cerebral cortex , 2001, Neuroscience.

[17]  J. M. Silvers,et al.  Prenatal cocaine alters dopamine and sigma receptor binding in nucleus accumbens and striatum in dams and adolescent offspring. , 2006, Neurotoxicology and teratology.

[18]  Qinqin Gao,et al.  Myo9b and RICS modulate dendritic morphology of cortical neurons. , 2013, Cerebral cortex.

[19]  Marta Coelho Antunes,et al.  The novel object recognition memory: neurobiology, test procedure, and its modifications , 2011, Cognitive Processing.

[20]  J. Topley,et al.  Behavioural, developmental and child protection outcomes following exposure to Class A drugs in pregnancy. , 2007, Child: care, health and development.

[21]  Pat Levitt,et al.  In Utero Cocaine-Induced Dysfunction of Dopamine D1 Receptor Signaling And Abnormal Differentiation of Cerebral Cortical Neurons , 2000, The Journal of Neuroscience.

[22]  Pat Levitt,et al.  Prenatal Exposure to Cocaine Produces Unique Developmental and Long-Term Adaptive Changes in Dopamine D1 Receptor Activity and Subcellular Distribution , 2007, The Journal of Neuroscience.

[23]  D. Tibboel,et al.  Withdrawal symptoms in children after long-term administration of sedatives and/or analgesics: a literature review. “Assessment remains troublesome” , 2007, Intensive Care Medicine.

[24]  S. Glatt,et al.  Prenatal cocaine exposure decreases nigrostriatal dopamine release in vitro: Effects of age and sex , 2004, Synapse.

[25]  Ying Chen,et al.  GRK5 promotes F-actin bundling and targets bundles to membrane structures to control neuronal morphogenesis , 2011, The Journal of cell biology.

[26]  S. Dey,et al.  Specificity of prenatal cocaine on inhibition of locus coeruleus neurite outgrowth , 2006, Neuroscience.

[27]  S. Minnes,et al.  Prenatal Tobacco, Marijuana, Stimulant, and Opiate Exposure: Outcomes and Practice Implications , 2011, Addiction science & clinical practice.

[28]  J. Howland,et al.  Altered object-in-place recognition memory, prepulse inhibition, and locomotor activity in the offspring of rats exposed to a viral mimetic during pregnancy , 2012, Neuroscience.

[29]  H. M. Geller,et al.  A Mechanism for the Inhibition of Neural Progenitor Cell Proliferation by Cocaine , 2008, PLoS medicine.

[30]  P. Kalivas Cocaine and amphetamine-like psychostimulants: neurocircuitry and glutamate neuroplasticity , 2007, Dialogues in clinical neuroscience.

[31]  W. Geber,et al.  Postpartum weight alteration in hamster offspring from females injected during pregnancy with either heroin, methadone, a composite drug mixture, or mescaline. , 1974, American journal of obstetrics and gynecology.