Date of Award

2021

Degree Name

Pharmaceutical Sciences

College

School of Pharmacy

Type of Degree

Pharm.D.

Document Type

Dissertation

First Advisor

Dr. Boyd R. Rorabaugh, Committee Chairperson

Second Advisor

Dr. Daniel A. Brazeau, Committee Member

Third Advisor

Dr. Eric R. Blough, Committee Member

Abstract

Methamphetamine (meth) is a synthetic stimulant, and its abuse is a significant public health concern in the United States and all over the world. Methamphetamine is a highly addictive drug, and its abuse is widespread among women of child-bearing age. The consequences of methamphetamine abuse are not only of relevance to pregnant women, but also their unborn children, as amphetamine type substances can cross the placental barrier and effect the fetus during gestation. Most previous studies investigating the impact of prenatal methamphetamine exposure on the offspring have focused on neurological and behavioral effects. The goal of this study was to investigate the impact of prenatal methamphetamine exposure on the cardiovascular system of adult offspring. Using a rat model, the primary finding of this work was that prenatal exposure to methamphetamine produces long-lasting and sex-dependent effects in the cardiovascular system of adult offspring. Specifically, prenatal exposure to methamphetamine hypersensitizes the female heart to ischemic injury regardless of whether exposure to methamphetamine occurs during the first or second half of the gestational period. Although this effect of prenatal methamphetamine persists in 2-month-old offspring, it subsides before 1 year of abstinence. This work also demonstrated that prenatal exposure to methamphetamine leads to perivascular adipose tissue dysfunction, disruption of NO signaling, and potentiation of angiotensin II-induced contraction of the aorta in a sex-dependent manner. These data demonstrate that prenatal exposure to methamphetamine produces sex-dependent effects in the heart and vasculature of offspring that persist into adulthood.

Subject(s)

Pregnant women -- Drug use -- United States.

Newborn infants -- Effect of drugs on -- United States.

Drug abuse in pregnancy -- United States.

Methamphetamine abuse -- United States.

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