The applicant is director of the Drug Abuse Program, started in 1997 at the Research Institute Neurosciences of the Free University in Amsterdam. This multidisciplinary research program currently evaluates the hypothesis that self-administration of addictive drugs may cause similar long-lasting neuroadaptive changes in the mesocorticolimbic system, resulting in a persistent hyper-responsiveness towards these drugs, environmental factors (cue's) and stressors and consequently in an enduring addiction prone state. This hypothesis is tested in rats and mice. The major aim of this research program is to define new pharmacotherapeutic targets in the brain of addicts and to provide the scientific basis for successful clinical trials. Our behavioural studies include analysis of acquisition of (intravenous) heroin, psychostimulant and (oral) ethanol self-administration as well as the reinstatement of (non-reinforced) drug-seeking behavior. Temporal changes in signal transduction processes are studied neurochemically and electrophysiologically in brain slices. Mesolimbic gene expression patterns are studied using differential display PCR, subtractive hybridization, cDNA microarrays and quantitative in situ hybridization histochemistry. Neuropeptide and protein synthesis is investigated by means of mass spectroscopy and nano-scale separation and detection techniques. Protein phosphorylation is studied using two-dimensional gel electrophoresis. Moreover, pharmacological (receptor (ant)agonists) and molecular biological (anti-sense and retroviral vector techniques, transgenic mice, inducible knockouts) interventions are used to reveal the causal relationships between addiction behavior and adaptive changes in neuronal communication.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
1R01DA013768-01
Application #
6291535
Study Section
Special Emphasis Panel (ZDA1-RXL-E (20))
Program Officer
Pollock, Jonathan D
Project Start
2001-03-01
Project End
2004-02-28
Budget Start
2001-03-01
Budget End
2002-02-28
Support Year
1
Fiscal Year
2001
Total Cost
$112,200
Indirect Cost
Name
Vrije Universiteit
Department
Type
DUNS #
409689361
City
Amsterdam
State
Country
Netherlands
Zip Code
1081 -HV