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Amygdala CRF in reduced anxiety and alcohol consumption in PKCepsilon null mice


Alcoholism, a major health issue worldwide, is characterized by high rates of relapse. Stress/anxiety probably contribute to relapse vulnerability and are the topic of this proposal.

To determine the role in addiction of novel genes such as PKCe, which is regulated by alcohol, behavioural analysis of knockout mice is required. During her PhD project, H.

Lesscher studied cocaine reinforcement in µ-opioid receptor mutant mice. With this, she was the first in the Rudolf Magnus Institute of Neuroscience to set up addiction-related research in mice. However, she and the laboratory would benefit from refinement of the behavioural paradigms, which is the rationale behind this application.

The host institute, Dr. Messing's laboratory at the Ernest Gallo Clinic and Research Centre, is well experienced with mouse behaviour, particularly anxiety and alcoholism.

This proposal will investigate amygdala CRF regulation in the context of alcohol withdrawal-induced anxiety and alcohol consumption in PKCe null mice. Recent studies in Dr. Messing's laboratory have shown that PKCe null mice are less anxious, consume less alcohol and display a reduced 'alcohol deprivation effect' as compared to wild-type mice.

Further, amygdala CRF, GABAA activity and plasma corticosterone deviate from wild-type. This proposal will therefore investigate, in PKCe null mice, the relation between alcohol withdrawal-induced anxiety and alcohol consumption and the underlying mechanisms.

Upon returning to the Netherlands, H. Lesscher will implement t he skills and experience gained to investigate opioid gene x environment interactions in drug reinforcement, thereby improving the competitiveness of European addiction researchers.

This international training at the Gallo Centre will further increase the probability of H. Lesscher receiving extramural funding to pursue her scientific career with an excellent research background applied to a field with high clinical relevance.


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