Date of Award

2013

Degree Type

Thesis

Degree Name

Master of Science in Biomedical Sciences

First Advisor

Adwoa D Aduonum, PhD

Second Advisor

H Keith Brown, PhD

Third Advisor

Kimberly Baker, PhD

Fourth Advisor

Sanika Chirwa, MD, PhD

Fifth Advisor

Brian M Matayoshi, PhD

Abstract

Methamphetamine (METH) is a highly addictive drug of abuse that has a severe impact on neuronal changes in the brain including modulations of plasticity, cognitive dysfunction, as well as memory impairment. These changes can be seen as modifications in the expression of biochemical markers associated with synaptic plasticity. One such marker associated with memory impairment is alpha synuclein (α-syn). Alteration of α-syn expression has been linked to memory impairment in patients with Alzheimer’s disease (AD) and Parkinson’s disease (PD). Here we assess the effect of chronic METH treatment in correlation to cognitive functions.

Twenty-nine guinea pigs (male, 150-250 g) were subcutaneously inserted with ALZET osmotic mini-pumps to deliver either a) saline (24 μl/day), b) METH (10 mg/kg) per day for 7 days or c) Post METH washout (10mg/kg) . On Day–7, the Novel Object Recognition test (NOR) was used to assess memory recall. Electrophysiological techniques were used to assess synaptic plasticity, in the hippocampus CA1 subfield, as it relates to learning and memory (n=6). Western blots were used to evaluate the expression of α-syn in the hippocampus. Saline treated animals (n=7) and the Post METH washout (n=12) showed a preference for the novel object as compared to the METH treated animals (n=10) that had a preference for the familiar object.even after 7 days post treatment (n=12). Molecular assays showed a down regulation of endogenous alpha synuclein protein levels in the hippocampus between subgroups. Furthermore, long-term potentiation (a cellular correlate of memory) was maintained in all subgroups.

The results from this study warrant the conclusion, that METH affects some of the same mechanisms underlining memory function and the drug-induced activation lead to the memory impairments observed in METH addicts and the role of alpha synuclein in the memory function still remains unclear.