Effects of prenatal cocaine exposure on early postnatal rodent brain structure and diffusion properties

Abstract

Prenatal cocaine exposure has been associated with numerous behavioral phenotypes in clinical populations, including impulsivity, reduced attention, alterations in social behaviors, and delayed language and sensory-motor development. Detecting associated changes in brain structure in these populations has proven difficult, and results have been inconclusive and inconsistent. Due to their more controlled designs, animal models may shed light on the neuroanatomical changes caused by prenatal cocaine; however, to maximize clinical relevance data must be carefully collected using translational methods. The goal of this study was two-fold: 1) determine if prenatal cocaine alters developmental neuroanatomy using methods that are available to human researchers, specifically structural MRI and diffusion tensor imaging; and 2) to determine the feasibility of rodent in vivo neuroimaging for usage in longitudinal studies of developmental disorders. Cocaine-exposed (prenatal days 1–20, 30mg/kg/day) rat pups were sedated and imaged live using diffusion tensor imaging and postmortem (fixed) using magnetic resonance histology on postnatal day 14. Volume and diffusion properties in whole brain as well as specific regions of interest were then assessed from the resulting images. Whole brain analyses revealed that cocaine-exposed animals showed no change in whole brain volume. Additionally, we found alterations in fractional anisotropy across regions associated with reward processing and emotional regulation, especially in the thalamus and globus palladus, as well as sex-dependent effects of cocaine in the right cortex. Reductions in fractional anisotropy were paired with reductions only in axial diffusivity, which preliminarily suggests that the changes observed here may be due to axonal damage, as opposed to reductions in myelination of the affected regions/pathways. Our data indicate that prenatal cocaine may target a number of developing brain structures, but does not result in overt changes to brain volumes. These results highlight not only the brain alterations that result from prenatal cocaine, but also the advancements in live imaging that allow longitudinal study designs in other models.

Longitudinal Effects of Embryonic Exposure to Cocaine on Morphology, Cardiovascular Physiology, and Behavior in Zebrafish

“…Use of model organisms allows carefully controlled administration of the cocaine to pregnant mothers and detailed analysis of cellular and molecular abnormalities associated with in utero drug exposure [ 11 , 12 , 13 , 14 ]. Decreased brain size has been demonstrated in rodents and monkeys treated with cocaine in utero [ 11 , 14 , 15 , 16 ]. Mice raised after in utero cocaine exposure have behavioral deficits [ 12 ] and acquire cocaine self-administration more quickly than untreated controls [ 17 ].…”

Prenatal cocaine exposure and its impact on cognitive functions of offspring: a pathophysiological insight

“…In contrast to the outcomes of the clinical studies of Rivkin et al (2008) and Grewen et al (2014), McMurray et al (2015 did not observe differences in total brain volume or in cortical regions in their latest experimental study of rats. These authors found, however, alterations in fractional anisotropy in regions that were associated with emotional regulation and reward processing.…”

“…Species-specific differences may account for the variation in outcomes observed in this study compared to the study of Grewen et al (2014) and McMurray et al (2015).…”

Use of fast-scan cyclic voltammetry to assess phasic dopamine release in rat models of early postpartum maternal behavior and neglect

“…Rats in the CC group were given twice daily injections of 15 mg/kg (s.c.) cocaine hydrochloride (Sigma, St. Louis, MO; dissolved in normal saline) at approximately 09:00 and 16:00 h, while UN rats were given no injections but were weighed and handled daily, as previously described (McMurray et al, 2015). …”

“…The 2013 National Survey on Drug Use and Health found that 5.4% of pregnant women in the US were using illicit drugs, including cocaine (SAMHSA 2014). Affecting both mother and fetus, prenatal cocaine use has linked to deficits in infant development and maternal care in humans (Burns et al, 1991; Kelley et al, 1991; Murphy et al, 1991; Williams-Petersen et al, 1994; Mayes et al, 1997; Strathearn and Mayes 2010; Rutherford et al, 2011; Cain et al, 2013; Liu et al, 2013; Chiriboga et al, 2014; Grewen et al, 2014) and in rats (Johns et al, 2005; McMurray et al, 2013; Zeskind et al, 2014; McMurray et al, 2015; Lippard et al, 2015). As cocaine targets monoamine transporters, including the dopamine transporter, phasic dopamine transmission in cocaine-exposed mothers may be compromised.…”