scholarly journals Alterations in excitatory and inhibitory synaptic development within the mesolimbic dopamine pathway in a mouse model of prenatal drug exposure

2020 ◽  
Author(s):  
Taylor Boggess ◽  
Hannah Sexton ◽  
Anna Mazur ◽  
Richard D. Egleton ◽  
Lawrence M. Grover ◽  
...  
Keyword(s):  
Mouse Model ◽  
Drug Exposure ◽  
Drugs Of Abuse ◽  
Prenatal Drug Exposure ◽  
Opioid Abuse ◽  
Mesolimbic Dopamine ◽  
Synaptic Development ◽  
Microscopy Imaging ◽  
The Mean ◽  
Mesolimbic Dopamine Pathway

AbstractThe rise in rates of opioid abuse in recent years has led to an increase in the incidence of neonatal abstinence syndrome (NAS). Despite having a greater understanding of NAS and its symptoms, there still remains a lack of information surrounding the long-term effects of prenatal exposure to drugs of abuse on neurological development. One potential outcome of prenatal drug exposure that has been increasingly explored is disruption in normal synaptogenesis within the central nervous system. Both opioids and gabapentin, an antiepileptic drug commonly co-abused by opioid abuse disorder patients, have been shown to interfere with the normal functioning of astrocytes, non-neuronal glial cells known to serve many functions, including regulation of synaptic development. The goal of this study was to investigate the effects of prenatal drug exposure on synaptogenesis within brain regions associated with the mesolimbic dopamine pathway, the primary reward pathway within the brain associated with drug abuse and addiction, in a pregnant mouse model. Immunohistochemistry (IHC) and confocal fluorescence microscopy imaging studies on the brains of postnatal day 21 (P21) mouse pups revealed a significant increase in the mean number of excitatory synapses within the anterior cingulate cortex (ACC), nucleus accumbens (NAc), and prefrontal cortex (PFC) in mice that were prenatally exposed to either the opioid drug buprenorphine or gabapentin. These studies also revealed a significant decrease in the mean number of inhibitory synapses within the NAc and PFC of mice treated with buprenorphine. This observed net increase in excitatory signaling capability within the developing mesolimbic dopamine pathway suggests that exposure to drugs of abuse in utero can trigger maladaptive neuronal connectivity that persists beyond the earliest stages of life.

scholarly journals Alterations in Excitatory and Inhibitory Synaptic Development Within the Mesolimbic Dopamine Pathway in a Mouse Model of Prenatal Drug Exposure

2021 ◽  
Vol 9 ◽  
Author(s):  
Taylor Boggess ◽  
James C. Williamson ◽  
Ethan B. Niebergall ◽  
Hannah Sexton ◽  
Anna Mazur ◽  
...  
Keyword(s):  
Mouse Model ◽  
Drug Exposure ◽  
Drugs Of Abuse ◽  
The United States ◽  
Prenatal Drug Exposure ◽  
Anterior Cingulate ◽  
Synaptic Connectivity ◽  
Long Term Effects ◽  
Mesolimbic Dopamine ◽  
Mesolimbic Dopamine Pathway

The rise in rates of opioid abuse in recent years in the United States has led to a dramatic increase in the incidence of neonatal abstinence syndrome (NAS). Despite improved understanding of NAS and its acute symptoms, there remains a paucity of information regarding the long-term effects of prenatal exposure to drugs of abuse on neurological development. The primary goal of this study was to investigate the effects of prenatal drug exposure on synaptic connectivity within brain regions associated with the mesolimbic dopamine pathway, the primary reward pathway associated with drug abuse and addiction, in a mouse model. Our secondary goal was to examine the role of the Ca+2 channel subunit α2δ-1, known to be involved in key developmental synaptogenic pathways, in mediating these effects. Pregnant mouse dams were treated orally with either the opioid drug buprenorphine (commonly used in medication-assisted treatment for substance use patients), gabapentin (neuropathic pain drug that binds to α2δ-1 and has been increasingly co-abused with opioids), a combination of both drugs, or vehicle daily from gestational day 6 until postnatal day 11. Confocal fluorescence immunohistochemistry (IHC) imaging of the brains of the resulting wild-type (WT) pups at postnatal day 21 revealed a number of significant alterations in excitatory and inhibitory synaptic populations within the anterior cingulate cortex (ACC), nucleus accumbens (NAC), and medial prefrontal cortex (PFC), particularly in the buprenorphine or combinatorial buprenorphine/gabapentin groups. Furthermore, we observed several drug- and region-specific differences in synaptic connectivity between WT and α2δ-1 haploinsufficient mice, indicating that critical α2δ-1-associated synaptogenic pathways are disrupted with early life drug exposure.

The Effects of HIV on Cognitive and Motor Development in Children Born to HIV-Seropositive Women With No Reported Drug Use: Birth to 24 Months

PEDIATRICS ◽  
1995 ◽  
Vol 96 (6) ◽  
pp. 1078-1082
Author(s):  
Caryl L. Gay ◽  
F. Daniel Armstrong ◽  
Donna Cohen ◽  
Shenghan Lai ◽  
Marjorie D. Hardy ◽  
...  
Keyword(s):  
Motor Development ◽  
Infant Development ◽  
Drug Exposure ◽  
Maternal Separation ◽  
Prenatal Drug Exposure ◽  
Control Group ◽  
Motor Functioning ◽  
Immunodeficiency Virus ◽  
The Mean ◽  
Hiv Seropositive

Objective. This study documents delays in the mental and motor functioning of infants perinatally infected with human immunodeficiency virus (HIV) while controlling for confounding effects of prenatal drug exposure, ethnicity, socioeconomic status, and maternal separation and death. Methods. The cognitive and motor development of 126 infants born to nondrug-using, HIV-seropositive Haitian women was assessed at 3-month intervals through 24 months of age using the Bayley Scales of Infant Development. By 18 months of age, 28 of the infants were diagnosed as HIV-infected, and the 98 uninfected infants served as a control group. The infected and uninfected infants did not differ with respect to mean gestational age, birth weight, ethnicity, or rates of maternal separation and death. Results. By 3 months of age, the mean mental and motor scores of the infected infants were significantly lower than those of the uninfected controls. Furthermore, the initial differences between the two groups increased over time, as many of the infected infants became increasingly delayed. Although the infected infants tended to perform more poorly than the uninfected infants, nearly one third of the infected infants exhibited relatively normal cognitive development and half demonstrated relatively normal motor development. Conclusions. Over the first 24 months of life, the mean rate of development of HIV-infected infants is significantly slower than that of noninfected infants born to seropositive mothers. This occurs even when the effects are not confounded with those of prenatal drug exposure.

A mouse model of early social interactions after prenatal drug exposure: a genetic investigation

1994 ◽  
Vol 113 (3-4) ◽  
pp. 388-394 ◽  
Author(s):  
Giovanni Laviola ◽  
Maria Livia Terranova ◽  
Kofi Sedowofia ◽  
Ruth Clayton ◽  
Aubrey Manning
Keyword(s):  
Mouse Model ◽  
Social Interactions ◽  
Drug Exposure ◽  
Prenatal Drug Exposure ◽  
Genetic Investigation

scholarly journals Demyelination and remyelination detected in an alternative cuprizone mouse model of multiple sclerosis with 7.0 T multiparameter magnetic resonance imaging

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shuang Ding ◽  
Yu Guo ◽  
Xiaoya Chen ◽  
Silin Du ◽  
Yongliang Han ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Multiple Sclerosis ◽  
Magnetic Resonance ◽  
Mouse Model ◽  
Diffusion Tensor ◽  
Mean Diffusivity ◽  
Blue Staining ◽  
Resonance Imaging ◽  
The Mean ◽  
Underlying Mechanisms

AbstractThe aim of this study was to investigate the mechanisms underlying demyelination and remyelination with 7.0 T multiparameter magnetic resonance imaging (MRI) in an alternative cuprizone (CPZ) mouse model of multiple sclerosis (MS). Sixty mice were divided into six groups (n = 10, each), and these groups were imaged with 7.0 T multiparameter MRI and treated with an alternative CPZ administration schedule. T2-weighted imaging (T2WI), susceptibility-weighted imaging (SWI), and diffusion tensor imaging (DTI) were used to compare the splenium of the corpus callosum (sCC) among the groups. Prussian blue and Luxol fast blue staining were performed to assess pathology. The correlations of the mean grayscale value (mGSV) of the pathology results and the MRI metrics were analyzed to evaluate the multiparameter MRI results. One-way ANOVA and post hoc comparison showed that the normalized T2WI (T2-nor), fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD) values were significantly different among the six groups, while the mean phase (Φ) value of SWI was not significantly different among the groups. Correlation analysis showed that the correlation between the T2-nor and mGSV was higher than that among the other values. The correlations among the FA, RD, MD, and mGSV remained instructive. In conclusion, ultrahigh-field multiparameter MRI can reflect the pathological changes associated with and the underlying mechanisms of demyelination and remyelination in MS after the successful establishment of an acute CPZ-induced model.

Pediatric Psychopharmacology and the Interaction between Drugs and the Developing Brain

1998 ◽  
Vol 43 (6) ◽  
pp. 582-584 ◽  
Author(s):  
Benedetto Vitiello
Keyword(s):  
Drug Exposure ◽  
Imaging Techniques ◽  
Quantitative Imaging ◽  
Adult Life ◽  
Prenatal Drug Exposure ◽  
Developing Brain ◽  
Teratogenic Effects ◽  
Pharmacological Agents ◽  
Early Inhibition ◽  
Interaction Between Drugs

With increasing frequency, psychotropic medications are being prescribed to young children, often for long periods of time. The interaction between psychotropics and the developing brain has not been systematically investigated in humans. Data collected from animals suggest that developing neurotransmitter systems can be exquisitely sensitive to early inhibition or stimulation by pharmacological agents, which can lead to permanent changes in adult life. Most of these data are collected from rodents, and their extrapolation to humans is difficult. More relevant models could be developed, for instance using primates. In humans, the focus of research has traditionally been on the possible teratogenic effects of prenatal drug exposure. Recently introduced quantitative imaging techniques can offer new approaches to studying the effects of psychotropics on the developing brain. This research has clear implications for the safety and efficacy of psychopharmacologic drug use in children.

Intelligence and School Readiness in Preschool Children With Prenatal Drug Exposure

2004 ◽  
Vol 10 (2) ◽  
pp. 89-101 ◽  
Author(s):  
Margaret B. Pulsifer ◽  
Krestin Radonovich ◽  
Harolyn M.E. Belcher ◽  
Arlene M. Butz
Keyword(s):  
Preschool Children ◽  
School Readiness ◽  
Drug Exposure ◽  
Prenatal Drug Exposure
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