Prenatal cocaine exposure increases anxiety, impairs cognitive function and increases dendritic spine density in adult rats: influence of sex

Abstract

Cocaine exposure during pregnancy can impact brain development and have long-term behavioral consequences. The present study examined the lasting consequences of prenatal cocaine (PN-COC) exposure on the performance of cognitive tasks and dendritic spine density in adult male and female rats. From gestational day 8 to 20, dams were treated daily with 30 mg/kg (ip) of cocaine HCl or saline. At 62 days of age, offspring were tested consecutively for anxiety, locomotion, visual memory and spatial memory. PN-COC exposure significantly increased anxiety in both sexes. Object recognition (OR) and placement (OP) tasks were used to assess cognitive function. Behavioral tests consisted of an exploration trial (T1) and a recognition trial (T2) that were separated by an inter-trial delay of varying lengths. Male PN-COC subjects displayed significantly less time investigating new objects or object location during T2 in both OR and OP tasks. By contrast, female PN-COC subjects exhibited impairments only in OR and only at the longest inter-trial delay interval. In addition, gestational cocaine increased dendritic spine density in the prefrontal cortex and nucleus accumbens in both genders, but only females had increased spine density in the CA1 region of the hippocampus. These data reveal that in-utero exposure to cocaine results in enduring alterations in anxiety, cognitive function and spine density in adulthood. Moreover, cognitive deficits were more profound in males than in females. Keywords sex differences; synaptic plasticity; prefrontal cortex; hippocampus; visual memory; spatial memory Cocaine abuse during pregnancy is recognized as a major social problem (G. A. Richardson, 1998; L. T. Singer et al., 2002). Clinical reports reveal an adverse relationship between Corresponding Author: Kaliris Salas-Ramirez, Department of Physiology and Pharmacology, 138th St and Convent Ave, New York, NY 10031, Tel: 212-650-8255; Fax: 212-650-7726; ksalasram@ccny.cuny.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Author ManuscriptNeuroscience. Author manuscript; available in PMC 2011 September 1. Less is known about gender-specific effects of gestational cocaine exposure, even though the effects of cocaine exposure in adulthood are sex-dependent in both rodents and humans (S. M. Evans and R. W. Foltin, 2009). For example, adult female subjects self-administer psychostimulants at lower doses than do males, drug use escalates more rapidly to dependence, and females are at greater risk for relapse following withdrawal than males (J. B. Becker and M. Hu, 2008). Fe...

High anxiety is a predisposing endophenotype for loss of control over cocaine, but not heroin, self-administration in rats

“…Additionally, exposure to, or withdrawal from, cocaine and heroin increases anxiety (Rogerio and Takahashi 1992;Schulteis et al 1998;Zhou et al 2003;Le Merrer et al 2006;Ambrose-Lanci et al 2010;Salas-Ramirez et al 2010).…”

Cocaína prenatal y consumo de cocaína de ratones adultos jóvenes

“…Los efectos perjudiciales de la EPC sobre el aprendizaje y memoria son bien conocidos por las modificaciones estructurales en regiones específicas asociadas a la cognición y en los ratones machos se presenta mayor impacto (Salas-Ramírez et al, 2010). Aparte de esto, no se tiene otra explicación respecto la falta de efectos de EPC 50 mg/kg/día en los machos, encontrada en el presente estudio.…”

“…Esta mayor vulnerabilidad de los ratones machos para el posterior autoconsumo, es consistente con los resultados de diferentes investigaciones (DDow-Edwards et al (2014);Peña-Oliver, 2007;Malanga et al, 2008;Rocha et al, 2002;Salas-Ramírez et al, 2010), en las que la EPC incrementó la autoadministración de drogas (cocaína, morfina, entre otras) únicamente en los machos en posteriores etapas de la vida, adolescencia o adultez.…”

“…Diversos estudios apoyan el abuso de drogas para reducir la ansiedad tanto en la adquisición como en el mantenimiento del consumo (Butler et al, 2014;Sinha, 2008). Además, la EPC produce mayor vulnerabilidad en los machos respecto a los daños en la emoción y en la cognición en animales (roedores) y es lo que se observa en la clínica (Salas-Ramírez et al, 2010).…”

“…La corteza orbitofrontal participa activamente en el control inhibitorio, por lo que los daños en esta estructura se van a evidenciar en la impulsividad característica de la conducta adictiva (Badanich, Becker, & Woodward, 2011;DePoy & Gourley, 2015;Malanga et al, 2008;Salas-Ramírez et al, 2010). Por otra parte, los roedores (ratones o ratas) en la adolescencia o la juventud temprana, tienen mayor probabilidad En este estudio se encontró una gran influencia de la EPC en la posterior conducta de consumo de cocaína en ratones, sobre todo en el mantenimiento, y los machos fueron los más afectados.…”