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The Effects of Early-Life Lead Exposure on Adult Delta9-Tetrahydrocannabinol Sensitivity, Self-administration, and Tolerance

Indiana University-Purdue University Indianapolis (IUPUI) / Environmental exposure to lead (Pb) and cannabis use are two of the largest public health
issues facing modern society in the United States and around the world. Exposure to Pb in early
life has been unequivocally shown to have negative impacts on development, and recent research
is mounting showing that it may also predispose individuals for risk of developing substance use
disorders (SUD). At the same time, societal and legal attitudes towards cannabis (main
psychoactive component delta-9-tetrahydrocannabinol) have been shifting, and many American
states have legalized the recreational use of cannabis. It is also the 3rd most widely used drug of
abuse in the US, and rates of cannabis use disorder are on the rise. This thesis sets out to
establish whether there is a link between early life Pb exposure and later THC-related behavior
in C57BL6/J mice, as has been demonstrated for other drugs of abuse. The first aim seeks to
answer whether Pb exposure affects physiological THC sensitivity (as measured by the
cannabinoid-induced tetrad). The second aim seeks to answer whether Pb exposure affects edible
THC self-administration and the development of THC tolerance (also measured by the tetrad). It
was hypothesized that Pb exposure would decrease THC sensitivity (Aim 1), would enhance
THC self-administration (Aim 2), enhance the development of THC tolerance (Aim 2), and
finally that sex-dependent effects of Pb-exposure and THC would be observed (Aims 1 & 2).
These hypotheses ended up not being supported, but Aim 1 produced findings indicating that
THC sensitivity was increased by Pb exposure, but only in female mice. Future research will
hopefully be able to fully explore the implications of these findings.

Identiferoai:union.ndltd.org:IUPUI/oai:scholarworks.iupui.edu:1805/30000
Date08 1900
CreatorsGarcy, Daniel
ContributorsBoehm, Stephen, Lapish, Christopher, Logrip, Marian
Source SetsIndiana University-Purdue University Indianapolis
Languageen_US
Detected LanguageEnglish
TypeThesis

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