Alcohol misuse is among the biggest social problems worldwide and the etiology of this complex disease is thus of great interest in basics science and medical research. The Diagnostic and Statistical Manual of Mental Disorder, 4th edition (DSM-IV) defines alcohol abuse as repeated use despite recurrent adverse consequences, characterized by a preoccupation with obtaining alcohol, loss of control over its consumption, development of tolerance, dependence, and impairment in social and occupational functioning.
Recent advances in addiction research, including the use of genetic animal models, are now providing some important insights into the cellular and molecular changes that occur in the brain after chronic drug consumption. Our research in this area has focused on the role of the endogenous opioid and cannabinoid systems. We have generated several mouse models in which the genes encoding for opioid peptides or opioid receptors have been deleted. Using these animal models, we have demonstrated that the opioid peptides modulate some of the rewarding and addictive properties of alcohol. Thus we observed that ethanol consumption was significantly reduced in the absence of β-endorphins, particularly in female knockout mice. Stress exposure, which is known to enhance alcohol drinking in humans, did not influence ethanol drinking in these mice and also did not alter ethanol consumption in enkephalin-deﬁcient mice. Interestingly, we also found an association of a variant in the gene that encodes human β-endorphin with alcohol dependence in women (Racz et al., 2008).
Within another project in our laboratory we identified gene loci or quantitative traits that contribute to the development and manifestation of alcohol addiction and related behaviors in mice (Drews et al., 2009). Here we combined high-throughput genotyping approaches and bioinformatics to show that the different traits observed in mouse models of alcoholism are obviously linked to numerous regions in the genome. This so-called QTL study also provided first data showing interaction patterns between alcohol-related traits, which were analyzed by interaction analyses (Figure 1).
Additionally, we are interested in the comorbidity of nicotine and schizophrenia, because the smoking incidence in schizophrenic patients is up to six times higher than in healthy people. It has been suggested that the patients use nicotine as a form of self-medication. Alternatively, it is possible that the rewarding or addictive properties of nicotine are enhanced in schizophrenic patients. We are investigating these hypotheses using genetic animal models of schizophrenia.
The projects are supported by the Bundesministerium für Bildung und Forschung (NGFN plus) and the Priority Program SPP1226 of the Deutsche Forschungsgemeinschaft (DFG).
Drews E, Racz I, Lacava AD, Barth A, Bilkei-Gorzo A, Wienker TF, Zimmer A. Quantitative trait loci contributing to physiological and behavioural ethanol responses after acute and chronic treatment. Int J Neuropsychopharmacol 2009:1-15.
Morse RM, Flavin DK. The definition of alcoholism. The Joint Committee of the National Council on Alcoholism and Drug Dependence and the American Society of Addiction Medicine to Study the Definition and Criteria for the Diagnosis of Alcoholism. JAMA 1992;268(8):1012-1014.
Racz I, Schurmann B, Karpushova A, Reuter M, Cichon S, Montag C, Furst R, Schutz C, Franke PE, Strohmaier J, Wienker TF, Terenius L, Osby U, Gunnar A, Maier W, Bilkei-Gorzo A, Nothen M, Zimmer A. The opioid peptides enkephalin and beta-endorphin in alcohol dependence. Biol Psychiatry 2008;64(11):989-997.