Research Overview

• Molecular analysis of post-mortem human and animal brain
  (genotyping, quantitative PCR, microarray, protein biochemistry, ChiP)
• In vivo monitoring of neurotransmission (microdialysis/HPLC)
• Human behavioral tests
• Rodent behavioral paradigms (drug self- administration, intolerance to delay task)
• Investigating the causal relationships between gene expression and behavior
  (viral gene manipulation and behavioral testing; transgenic animals)

The research group investigates the neurobiology underlying drug abuse and related psychiatric disorders. The work is focused on the systematic study of the human brain of drug abusers and subjects with psychiatric disorders in relation to opioid neuropeptide, cannabinoid, and dopamine neuronal systems. Drug abuse and, e.g., major depression are associated with alterations of mood, cognition, and motivation, thus, an important goal is to identify and map specific genes in the mesocorticolimbic system, which regulate emotional function.

Techniques such as in situ hybridization, RT-PCR, DNA microarray, in vitro autoradiography, and general biochemical assays are used for the detailed analyses of genes, and respective protein products, in discrete mesocorticolimbic brain areas. Molecular, biochemical, and in vivo studies of the human brain are assessed in relation to individual genotype in order to identify neurobiological correlates of functional genetic polymorphisms linked to addiction and affective disorders. Epigeneic mechanisms, e.g., DNA methylation, are also evaluated in relation to the regulation of gene expression.

A significant area of investigation is related to assessing the impact of prenatal drug exposure on human fetal brain development that may enhance later risk for substance abuse and psychiatric disturbances. Recent collaborative efforts involve in vivo imaging of the developing mesocorticolimbic system to examine the neurobiological association between behavioral traits (e.g., inhibitory control deficit) that appear to increase risk for substance abuse disorders.

As complement to studies of the human brain, animal models are used to examine in vivo neurotransmitter levels (e.g., dopamine as measured by the microdialysis technique) in discrete mesocorticolimbic brain areas during, e.g., operant drug self-administration behavior. The animal studies are designed to mimic the prenatal and adolescent drug exposure (particularly cannabis) seen in humans, and subsequent adult behaviors are linked to in vivo neurochemical fluctuations as well as molecular and biochemical events in the same subject.