Behavioral sensitization to ethanol: Neural basis and factors that influence its acquisition and expression.

Ethanol-induced behavioral sensitization (EBS) was first described in 1980, approximately 10 years after the phenomenon was described for psychostimulants. Ethanol acts on γ-aminobutyric acid (GABA) and glutamate receptors as an allosteric agonist and antagonist, respectively, but it also affects many other molecular targets. The multiplicity of factors involved in the behavioral and neurochemical effects of ethanol and the ensuing complexity may explain much of the apparent disparate results, found across different labs, regarding ethanol-induced behavioral sensitization. Although the mesocorticolimbic dopamine system plays an important role in EBS, we provide evidence of the involvement of other neurotransmitter systems, mainly the glutamatergic, GABAergic, and opioidergic systems. This review also analyses the neural underpinnings (e.g., induction of cellular transcription factors such as cyclic adenosine monophosphate response element binding protein and growth factors, such as the brain-derived neurotrophic factor) and other factors that influence the phenomenon, including age, sex, dose, and protocols of drug administration. One of the reasons that make EBS an attractive phenomenon is the assumption, firmly based on empirical evidence, that EBS and addiction-related processes have common molecular and neural basis. Therefore, EBS has been used as a model of addiction processes. We discuss the association between different measures of ethanol-induced reward and EBS. Parallels between the pharmacological basis of EBS and acute motor effects of ethanol are also discussed.

New pharmacological treatment strategies for relapse prevention.

Here we discuss treatment strategies that are based on pharmacological interventions to reduce craving and relapse in alcohol-dependent patients. We will first provide a historical overview about relapse prevention strategies. We will then review the development of disulfiram, naltrexone, acamprosate, and nalmefene and discuss their neurobiological modes of action. Then the concept of convergent genomic analysis will be introduced for the discovery of new molecular treatment targets. Finally, we will provide convincing evidence for the use of N-methyl-D-aspartate (NMDA) receptor channel blockers as substitution drugs. Important conclusions of this review are: (i) learning from other addictive substances is very helpful-e.g., substitution therapies as applied to opiate addiction for decades could also be translated to alcoholics, (ii) the glutamate theory of alcohol addiction provides a convincing framework for the use of NMDA receptor antagonists as substitution drugs for alcohol-dependent patients, (iii) a combination of behavioral and pharmacological therapies may be the optimal approach for future treatment strategies-one promising example concerns the pharmacological disruption of reconsolidation processes of alcohol cue memories, (iv) given that many neurotransmitter systems are affected by chronic alcohol consumption, numerous druggable targets have been identified; consequently, a "cocktail" of different compounds will further improve the treatment situation, (v) in silico psychopharmacology, such as drug repurposing will yield new medications, and finally, (vi) the whole organism has to be taken into consideration to provide the best therapy for our patients. In summary, there is no other field in psychiatric research that has, in recent years, yielded so many novel, druggable targets and innovative treatment strategies than for alcohol addiction. However, it will still be several years before the majority of the "treatment-seeking population" will benefit from those developments.

Alcohol withdrawal syndrome.

In susceptible patients, alcohol withdrawal syndrome (AWS) is often precipitated by other medical or surgical disorders, and AWS can adversely affect the course of these underlying conditions. Although the mortality rate of AWS has decreased over the past few decades, significant risk for morbidity and death remain if management is complicated by a variety of conditions. This review of AWS focuses on the scope of the clinical problem, historical features, pathophysiology, clinical presentation, and approaches to therapy, with particular emphasis on severe AWS that requires management in the intensive care unit.

Contrasting medical models of alcohol problems in Victoria around 1900.

AIMS: This paper examines four specialist medical inebriety institutions in Victoria, Australia between 1870 and 1930, which positioned themselves in distinct ways. It analyses how the treatment in each institution was located within wider medical approaches and contemporary medical ideas and practice. METHODS: Medical journals and texts, newspaper articles, government reports and institutional archives are used in the analysis. FINDINGS AND CONCLUSIONS: Alcohol treatment institutions in the late 19th and early 20th centuries were of several types, differentiated according to treatment approaches and their underlying premises as to the nature of the disease being treated, the particular patient groups for which they catered and their funding models and capacity to take patients committed for treatment under legislation. The institutional types identified in other Anglophone countries in this period can be extended to Australia, with some local variations in the timing of the appearance of the models, the longevity of institutions and gender of patients. In Australia there was no tradition of mutual patient support, as seen at the time in the United States. Each institution represented itself differently, in particular in terms of its particular medical model, although the treatments in practice differed less than in theory. The models employed allowed each institution to position itself in relation to trends in medical theory and practice, in particular to different conceptualizations of the type of disease being treated. Evaluating treatment models for alcohol problems in terms of medical theory and practice of the time can explain contrasting approaches.

Conversation with Raul Caetano.

In this occasional series we record the views and personal experience of people who have especially contributed to the evolution of ideas in the Journal's field of interest. Raul Caetano qualified in medicine in Brazil. While retaining close academic and cultural links with his native country, he has developed a career as an alcohol epidemiologist with research positions first in Berkeley,California and then at the University of Texas. He has contributed very widely to epidemiological research on drinking but with a sustained ability to develop the important ethnic dimensions of such studies.

What are the policy lessons of National Alcohol Prohibition in the United States, 1920-1933?

National alcohol prohibition in the United States between 1920 and 1933 is believed widely to have been a misguided and failed social experiment that made alcohol problems worse by encouraging drinkers to switch to spirits and created a large black market for alcohol supplied by organized crime. The standard view of alcohol prohibition provides policy lessons that are invoked routinely in policy debates about alcohol and other drugs. The alcohol industry invokes it routinely when resisting proposals to reduce the availability of alcohol, increase its price or regulate alcohol advertising and promotion. Advocates of cannabis law reform invoke it frequently in support of their cause. This paper aims: (i) to provide an account of alcohol prohibition that is more accurate than the standard account because it is informed by historical and econometric analyses; (ii) to describe the policy debates in the 1920s and 1930s about the effectiveness of national prohibition; and (iii) to reflect on any relevance that the US experience with alcohol prohibition has for contemporary policies towards alcohol. It is incorrect to claim that the US experience of National Prohibition indicates that prohibition as a means of regulating alcohol is always doomed to failure. Subsequent experience shows that partial prohibitions can produce substantial public health benefits at an acceptable social cost, in the absence of substantial enforcement.

The trouble with drink: why ideas matter.

This paper builds upon the work of previous authors who have explored the evolution of ideas in the alcohol arena. With revisions in the relevant sections of ICD and DSM forthcoming, such matters are of considerable contemporary importance. The focus here will be upon the history of the last 200 years. The main themes to be explored include the flux of ideas on what, over time, has counted as the trouble with drink, ideas on the cause of the problem and the impact of this thinking on public action. Medical authorities of the late Enlightenment period made the revolutionary suggestion that habitual drunkenness constituted a disease, rather than a vice. The thread of that idea can be traced to the present day, but with an alternative perception of drink itself or alcohol-related problems generally, as cause for concern, also having a lineage. There are several inferences to be drawn from this history: the need for vigilance lest disease formulations become stalking-horses for moralism and social control, the need to integrate awareness of alcohol dependence as a dimensional individual-level problem, with a public health understanding of the vastly amorphous and at least equally important universe of alcohol-related problems; the dangers lurking in scientific reductionism when the problems at issue truly require a multi-disciplinary analysis; and the need for global consensus rather than cultural imposition of ideas on what counts as the problem with drink.

Alexander's (356-323 BC) expeditionary Medical Corps 334-323 BC.

Alexander had a profound interest in medicine and healing. Original Greek texts survive mainly from the works of Plutarch and Arrian. This paper examines original sources naming the physicians who participated in Alexander's expedition in Asia, the battle injuries he sustained and his final illness in Babylon.

What killed Alexander the Great?

The cause of the death of the Macedonian King, Alexander the Great, at Babylon in 323 BC has excited interest and conjecture throughout the ages. The information available in the surviving ancient sources, none of which is contemporaneous, has been reviewed and compared with modern knowledge as set out in several well-known recent surgical texts. The ancient sources record epic drinking by the Macedonian nobility since at least the time of Phillip II, Alexander's father. Alexander's sudden illness and death is likely to have resulted from a surgical complication of acute alcoholic excess.