Pharmacology and toxicology
University of Eastern Finland,
With the goal of understanding the pathology of extensive alcohol consumption to the brain we have used post-mortem brains of Cloninger type 1 and 2 alcoholics as a research material for nearly 20 years. The methods used include Whole-Hemisphere Autoradiography for neurotransmitter receptor expression analyses and Mass Spectrometry studies for detection of endocannabinoid and steroid concentrations. As main findings, GABAergic and serotonergic changes separate alcoholics from controls. Main separating features for type 1 alcoholics have been decreased dopamine transporter, mu-opiod receptor and anandamide levels. Type 2 alcoholics have showed increased levels of glutamatergic receptors and decreased levels of serotonergic receptors. In addition to nucleus accumbens, brain areas relevant to social cognition have been repeatedly highlighted in the analyses, moving the focus of interpretation more firmly into psychobiosocial paradigm.
For post mortem material, it is important to weight the pros and cons, and I will summarize the lessons learned over the projects. The number of samples is small, 9, 8 and 10 for Cloninger type 1 and 2 alcoholics and non-alcoholic controls, respectively. Ante- and post-mortem effects could influence the results, the medical records are never complete, and furthermore, the use of post-mortem brain samples does not enable any determination of causality i.e. are the measured differences seen between alcoholics and controls caused by alcohol consumption or do they pre-exist and make the individual susceptible to suffer the alcoholism. However, using a set of post-mortem samples enables to perform a large series of studies for same individual subjects, and the analyses can be somewhat reliably compared to each other for more complete understanding of the neurochemistry than what is possible with in vivo experiments.