Bradley J. Martin

B.S. in Psychology, Colorado State University

Thesis Advisor: Howard Gu

E-Mail:  martin.1506@osu.edu

Research:

Repeated exposure to cocaine increases the density of dendritic spines on medium spiny neurons in the nucleus accumbens (NAC) and pyramidal cells in the medial prefrontal cortex (PFC). These structural changes are thought to underlie the long-lasting abnormalities in reward and cognition that are associated with cocaine addiction. Although cocaine binds to many targets, cocaine's ability to inhibit the dopamine transporter is particularly important for cocaine addiction; however, it is unknown whether this action is important for cocaine-induced increases in spine density. Our lab has developed genetically engineered mice that express a functional, but cocaine insensitive, dopamine transporter (DAT-CI). Unlike dopamine transporter knockout mice, DAT-CI mice have largely intact dopaminergic transmission, which we have shown is essential for elucidating the role of DAT inhibition in cocaine addiction. In this study, we will use DAT-CI mice to investigate the role of DAT inhibition in cocaine-induced structural plasticity. To test this, we will measure spine density in the nucleus accumbens and prefrontal cortex of DAT-CI mice after 2 weeks of cocaine (30 mg/kg, i.p.) administration with Golgi-Cox techniques. Since high levels of DAT are found in the nucleus accumbens and low levels are found in the PFC, we hypothesize that cocaine's ability to inhibit the dopamine transporter is necessary for increasing spine density in the NAC but is not necessary for increasing spine density in the PFC. This study may suggest that cocaine induced alterations in synaptic connectivity in areas of the brain associated with reward and cognition occur through different binding sites.

Publications:

Bruno JP, Gash C, Martin B, Zmarowski A, Pomerleau F, Burmeister J, Huettl P, and Gerhardt GA (2006) Second-by-second measurement of acetylcholine release in prefrontal cortex.  European Journal of Neuroscience; 24(10), 2749-57.

Wendland JR, Martin BJ, Kruse MR, Lesch KP and Murphy DL (2006) Simultaneous genotyping of four functional loci of human SLC6A4, with a reappraisal of 5-HTTLPR and rs25531.  Mol Psychiatry; 11(3):224-6.

Kim DK, Tolliver TJ, Huang SJ, Martin BJ, Andrews AM, Wichems C, Holmes A, Lesch KP, and Murphy DL (2005) Altered serotonin synthesis, turnover and dynamic regulation in multiple brain regions of mice lacking the serotonin transporter. Neuropharmacology; 49(6):798-810.

Presentations at National Meetings:

Sensory – and drug-induced cortical acetylcholine release on a second-by-second basis in freely-by-second basis in freely moving rats.  Society for Neuroscience, Atlanta, Georgia, 2006.