Bidirectional Modulation of Alcohol-Associated Memory Reconsolidation through Manipulation of Adrenergic Signaling.

Alcohol addiction is a problem of great societal concern, for which there is scope to improve current treatments. One potential new treatment for alcohol addiction is based on disrupting the reconsolidation of the maladaptive Pavlovian memories that can precipitate relapse to drug-seeking behavior. In alcohol self-administering rats, we investigated the effects of bidirectionally modulating adrenergic signaling on the strength of a Pavlovian cue-alcohol memory, using a behavioral procedure that isolates the specific contribution of one maladaptive Pavlovian memory to relapse, the acquisition of a new alcohol-seeking response for an alcohol-associated conditioned reinforcer. The β-adrenergic receptor antagonist propranolol, administered in conjunction with memory reactivation, persistently disrupted the memory that underlies the capacity of a previously alcohol-associated cue to act as a conditioned reinforcer. By contrast, enhancement of adrenergic signaling by administration of the adrenergic prodrug dipivefrin at reactivation increased the strength of the cue-alcohol memory and potentiated alcohol seeking. These data demonstrate the importance of adrenergic signaling in alcohol-associated memory reconsolidation, and suggest a pharmacological target for treatments aiming to prevent relapse through the disruption of maladaptive memories.This work was supported by a UK Medical Research Council Programme Grant (G1002231) to BJE and ALM and was conducted in the Behavioural and Clinical Neuroscience Institute (BCNI), an initiative jointly funded by the MRC and the Wellcome Trust. MJWS was supported by an MRC Doctoral Training Grant and the James Baird Fund at the Medical School of the University of Cambridge. ALM was partly supported by a BCNI lectureship and the Ferreras-Willetts Fellowship from Downing College, Cambridge.This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/npp.2015.24

The role of varenicline on alcohol-primed self-administration and seeking behavior in rats

RATIONALE: Varenicline, a smoking-cessation agent, may be useful in treating alcohol use disorders. An important consideration when studying factors that influence drinking/relapse is influence of the pharmacological effects of alcohol on these behaviors. Pre-exposure to alcohol (priming) can increase craving, drinking and seeking behaviors. OBJECTIVES: The primary goal of this work was to determine the effects of varenicline on alcohol-primed self-administration and seeking behavior in male Long Evans rats. METHODS: First, we assessed whether varenicline (0, 0.3, 1, 3 mg/kg, IP) has alcohol-like discriminative stimulus effects and whether varenicline alters sensitivity to alcohol in rats trained to discriminate a moderate alcohol dose (1 g/kg, IG) vs. water. Second, animals trained to self-administer alcohol underwent assessments to test the effects of: (i) varenicline (0, 0.3, 1, 3 mg/kg, IP) on self-administration, (ii) alcohol priming (0, 0.3, 1 g/kg, IG) on self-administration and seeking behavior, (iii) varenicline (1 mg/kg) in combination with alcohol priming (1 g/kg) on these behaviors. RESULTS: Varenicline did not substitute for alcohol, but disrupted the expression of sensitivity to alcohol. Varenicline decreased self-administration, but only at a motor impairing dose (3 mg/kg). Alcohol priming decreased self-administration and seeking behavior. Varenicline (1 mg/kg) blocked this effect under self-administration conditions, but not seeking conditions, which effectively resulted in increased alcohol intake. CONCLUSIONS: These findings suggest the importance of further behavioral and mechanistic studies to evaluate the use of varenicline in treating alcohol use disorders and its potential impact on drinking patterns in smokers using varenicline as a smoking cessation aid

Q fever (Coxiella burnetii): A bleuprint for outbreak

About 80 years ago, Q fever research began due to human outbreaksof unknown origin, associated with domestic animals. Since then, some but notall characteristics of this “query” disease, caused by the intracellular bacteriumCoxiella burnetii were revealed. In this chapter the bacteriology of the bacterium,clinical presentation, epidemiology and transmission of the disease in humans andanimals are presented. Domestic small ruminants are the main source of humanQ fever. Although Q fever is considered to be an occupational disease, outbreakshave a major public health impact and attract most attention. The Dutch Q feveroutbreak, involving 4000 human cases over the years 2007–2010, is an exampleof how Q fever can re-emerge from an endemic state into an outbreak of unforeseen dimension. In this outbreak the epidemiological link between dairy goats and human cases was confirmed by genotyping for the first time. This was possible due to the previous development of genotyping assays that are applicable on clinical material. Although Q fever seems to be a blue print for outbreaks it is not known yet what factors are essential to cause outbreaks and how they interact. To prevent outbreaks, a better understanding of these factors and their interaction is necessary and research should therefore focus on this