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Involvement of striatal and hippocampal sigma receptors in methamphetamine‐induced maladaptation
Author(s) -
Fennell Ashley Monique,
Swant Jarod,
Ansah Twum,
Goodwin J. Shawn,
Khoshbouei Habibeh
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.619.12
Methamphetamine, a substrate for the dopamine transporter, is a powerful psychostimulant, known for its capacity to decrease dopamine uptake and to release dopamine from intra‐neuronal stores via the reverse transport process. Chronic methamphetamine exposure is neurotoxic and can cause long‐lasting alterations in synaptic transmission and behavioral sensitization‐ phenomenon implicated in the development of psychosis in humans. Sigma (ó) receptors are found on dopaminergic neurons and have been hypothesized to modulate dopaminergic neurotransmission. Methamphetamine preferentially interacts with the ó1 receptor, and blockade of ó receptors diminishes methamphetamine‐induced hyper‐locomotion in rats. The long term goal of this project is to test the hypothesis that chronic methamphetamine exposure is neurotoxic and decreases working memory via a mechanism dependent on hippocampal sigma one receptor activation. The project is divided into two phases: phase I determines the electrophysiological, behavioral, and molecular effects of chronic methamphetamine exposure and the involvement of sigma receptors in these responses. In Phase II we will utilize an in vitro model system to investigate the underlying cellular mechanism(s) of methamphetamine and sigma receptor interaction.