Date of Award

2020

Document Type

Honors Thesis (Open Access)

Department

Colby College. Psychology Dept.

Advisor(s)

Melissa Glenn

Abstract

Choline is an essential dietary nutrient essential to the development and function of the central nervous system. Prenatal choline deficiency alters hippocampal development as well as acetylcholine metabolism, leading to cognitive impairments and attentional and sensory processing deficits into adulthood. MK-801 is an NMDA receptor antagonist frequently used in rodent models of neuropsychiatric conditions, particularly schizophrenia. Acutely and sub- chronically, it causes hyperlocomotion and social withdrawal. One primary goal of the present study were to investigate prenatal choline deficiency induces a biological vulnerability to the motor deficits, anhedonia, and social impairment precipitated by low-dose sub-chronic MK-801 administration in adulthood. Another goal was to illustrate any sex differences that exist in response to this treatment. Using the saccharin preference task, we found that deficient-fed males administered MK-801 had a diminished preference during test 2, but the effects of drug and diet condition were inconsistent overall and across sex. In motor assessments immediately following injection with MK-801 or saline, males and females injected with MK-801 demonstrated motor impairment across three dimensions. Females sustained this level of impairment throughout the course of injections. Taken together, the results of this study suggest that prenatal choline deficiency may represent a vulnerability to MK-801 induced anhedonia in males. Females are also affected to a greater degree by this neurotoxic treatment, as indicated by motor responses to acute and sub-chronic administration. This research contributes to the existing body of research investigating the effect of prenatal choline availability and pharmaceutical treatment on the expression of symptoms relevant to schizophrenia.

Keywords

nutrition, two-hit, negative symptoms, MK-801

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