MAILMAN RESEARCH CENTER

Behavioral Genetics Laboratory

Behavioral Genetics Laboratory Figure 1

Figure 1.  We use behavioral and molecular tools to understand how long-term exposure to drugs of abuse changes the brain.  Once animals are dependent on a drug such as cocaine or morphine, the brain operates at a new set point that requires the presence of drug for normal functioning.  During withdrawal or abstinence, the brain’s carefully controlled equilibrium is dramatically upset, leading to a myriad of withdrawal effects that include severe depression, anxiety, irritability and stress.  In many cases, these negative mood states are a driving force for relapse.  We have demonstrated using behavioral pharmacology that the neuropeptide dynorphin is necessary for some of these drug-dependent negative affective states.  We are currently asking how dynorphin regulates plasticity within the nucleus accumbens, a brain region critical for processing information related to reward and aversion.
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Behavioral Genetics Laboratory Figure 1

Figure 2.  To explore the molecular substrates of drug dependence and withdrawal, we use several molecular techniques.  We are initiating studies using herpes simplex virus (HSV) to deliver cDNAs encoding the signaling molecule ERK and a dominant negative form of ERK.  We also use quantitative real-time PCR (qRT-PCR) to measure gene expression in select brain regions.  By using Western blot analysis of phosphorylated proteins such as P-ERK, we can ask how behavioral manipulations affect signal transduction pathways on a rapid timescale.
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