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Assessing mechanisms driving increased nicotine use in schizophrenia using the MAM rodent model

Weeks, Jillian (2020) Assessing mechanisms driving increased nicotine use in schizophrenia using the MAM rodent model. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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Rates of smoking are 2-3 times higher among individuals with schizophrenia relative to the general population, posing a significant exacerbation of health and socioeconomic disparities. While the cause of this elevation is unknown, two prevalent hypotheses are that nicotine, the primary reinforcing component in cigarettes, is particularly rewarding to individuals with schizophrenia, or that these smokers smoke in an attempt to “self-medicate” their symptoms. The present study utilized the methylazoxymethanol (MAM) neurodevelopmental rodent model of schizophrenia to evaluate these hypotheses. In order to explore the “reinforcement hypothesis”, MAM and control (CTL) animals were allowed to self-administer nicotine across a range of doses and responding and intake of nicotine were compared. The “self-medication” hypothesis was evaluated by examining the effects of acute and chronic nicotine on several established behavioral paradigms known to be disrupted in the MAM model. Additionally, the effects of acute and chronic nicotine on neurophysiological dysfunction, including elevated VTA dopamine population activity and elevated ventral hippocampal (vHipp) activity, were observed. Our findings demonstrated that self-administration of nicotine, alone or in combination with another reinforcer, was not increased in MAM rats, suggesting that schizophrenia pathophysiology modeled by MAM does not confer increased nicotine reinforcement. Conversely, we observed nicotine-induced improvements in prepulse inhibition of startle and novel object recognition among MAM rats, as well as a normalization of elevated VTA dopamine and vHipp neuronal activity in these animals. Together, these findings lend greater support for a “self-medication” hypothesis behind increased smoking in schizophrenia and illustrate the potential utility of nicotinic modulation in future pharmacotherapies for certain schizophrenia symptoms.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Weeks, Jillianjillian.j.weeks@gmail.comjjw810000-0002-0795-9121
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee MemberSesack,
Committee ChairSved,
Committee MemberTorregrossa,
Committee MemberGrace,
Committee MemberMcClung,
Committee MemberSchmidt,
Date: 16 September 2020
Date Type: Publication
Defense Date: 26 May 2020
Approval Date: 16 September 2020
Submission Date: 16 July 2020
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Number of Pages: 143
Institution: University of Pittsburgh
Schools and Programs: Dietrich School of Arts and Sciences > Neuroscience
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: schizophrenia, nicotine, MAM model, dopamine, self-administration
Date Deposited: 16 Sep 2020 15:22
Last Modified: 16 Sep 2020 15:22


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