Date of Completion

Spring 5-1-2018

Thesis Advisor(s)

John Salamone

Honors Major

Physiology and Neurobiology

Disciplines

Biological Psychology | Mental Disorders | Psychiatric and Mental Health

Abstract

Effort-related decision making tasks in animals can model motivational symptoms in humans, which are a set of symptoms spanning a multitude of neuropsychiatric disorders, such as major depressive disorder and the negative symptoms of schizophrenia. The present studies aimed to evaluate the effort-related effects of the Val158Met polymorphism of human catechol-methyltransferase (COMT), by testing mice carrying either the human COMT Val (n=8) or Met allele (n=8) with Wild-Type control mice (n=15) by using concurrent FR2 and FR4/pellet choice tasks in a touchscreen operant conditioning apparatus. The Val158Met polymorphism has been repeatedly associated with neuropsychiatric disorders, and the Val allele has been associated with negative symptoms of schizophrenia. Additionally, the effort-related effects of the dopamine D2 antagonist, haloperidol, a drug used to treat positive symptoms of schizophrenia, but often inducing motivational side effects, was assessed in these transgenic mice. Haloperidol (0.05-0.15 mg/kg IP) decreased selection of the high effort/high reward option by reducing panel pressing across all genetic groups for both fixed ratio tasks. Furthermore, with the human COMT Val allele had significantly reduced panel pressing compared to Wild-Type mice. This study further validates the role of dopaminergic transmission in effort-related decision making, and supports the idea that the human COMT Val allele may be involved in negative symptoms of schizophrenia.

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