Heidi M.B. Lesscher
Dept. Neuroscience and Pharmacology
Section Neurobiology of Behaviour Function
Tel: +31 88 756 8844
Dr. L.J.M.J. Vanderschuren Title research
Neurogenetic mechanisms of alcoholism. Summary research
My research interests evolved from cocaine sensitivity, the topic of my thesis (2004) to the neurogenetics of alcoholism. I am particularly interested in individual (genetic) differences in susceptibility to develop alcoholism and in the neurobiological processes that underlie the development of excessive alcohol use and ultimately alcoholism. As a postdoc at the Ernest Gallo Clinic and Research Center (UCSF) in San Francisco I studied the role of amygdala protein kinase C epsilon (PKCε) signalling in anxiety and alcohol consumption, a project that was funded by a Marie Curie Fellowship. I used RNA interference to show that amygdala PKCε controls anxiety through regulation of amygdala CRF (Lesscher et al, 2008). Moreover, using a novel paradigm which we have termed the limited access choice paradigm, I showed that amygdala PKCε signalling is also important for the development of high ethanol intake and preference. With funding from the Brain Foundation of the Netherlands and a VENI grant from ZonMw, my current research projects aim to (1) identify genetic loci for high ethanol intake and/or preference in the limited access choice paradigm and (2) identify and characterize molecular pathways in the amygdala that determine the development of high ethanol intake and preference. Publications
H.M.B. Lesscher, M.J. Wallace, L. Zeng, V. Wang, J.K. Deitchman, T. McMahon, R.O. Messing, P.M. Newton, 2009. Amygdala protein kinase C epsilon controls alcohol consumption. Genes Brain and Behavior, in press.
H.M.B. Lesscher, T. McMahon, A.W. Lasek, W.H. Chou, J. Connolly, V. Kharazia,
R.O. Messing, 2008. Amygdala protein kinase C epsilon regulates corticotrophin
releasing factor and anxiety-like behavior. Genes Brain and Behavior, 7(3): 232-233.
D.S. Choi, W. Wei, J.K Deitchman, V.N. Kharazia, H.M.B. Lesscher, T. McMahon, D. Wang, Z.H. Qi, W. Sieghart, C. Zhang, K.M. Shokat, I. Mody, R.O. Messing, 2008. Protein kinase C delta regulates ethanol intoxication and enhancement of GABA-stimulated tonic current. Journal of Neuroscience, 28(46): 11890-11899.
H.M.B. Lesscher, M. Hordijk, N.P. Bondar, O.V. Alekseyenko, J. P.H. Burbach, J.M. van Ree, M.A.F.M. Gerrits, 2005. µ-Opioid receptors are not involved in acute cocaine-induced locomotor activity nor in development of cocaine-induced behavioural sensitization. Neuropsychopharmacology, 30(2): 278-285.
D.S. Mathon, H.M.B. Lesscher, M.A.F.M. Gerrits, A. Kamal, J.E. Pintar, A.G.P. Schuller, M.P. Smidt, B.M. Spruijt, J.P.H. Burbach, M.P. Smidt, J.M. van Ree, G.M.J. Ramakers, 2005. Increased GABAergic input to ventral tegmental area dopaminergic neurons associated with decreased cocaine reinforcement in µ-opioid receptor knockout mice. Neuroscience, 130(2): 359-367.