Genetic and environmental influences are both known to be causal factors in the development and maintenance of obesity. Stress related chronic stimulation of the hypothalamic-pituitary-adrenal (HPA) axis and resulting increased glucocorticoid exposure is known to be an important pathophysiological mechanism in the development of obesity. We show that the natriuretic peptide system, that mediates endocrine and behavioural responses to stress, plays a role in the control of long-term body weight in chronically ethanol drinking mice. In mice lacking functional NPR-A receptors, physical, and in particular psychological stress leads to enhanced and continuous increase in body weight in homozygote NPR-A mice. The effect of repeated stress on body weight appeared rapidly and persisted throughout life. Over a longer period of time without stress, body weights do not differ between the different genotypes. Moreover, we could demonstrate that NPR-A homozygote mice show significant higher corticosterone levels following stress. Heterozygote animals show an intermediate phenotype concerning body weights and corticosterone levels following stress. Alterations in the NPR-A receptor gene may constitute a genetic risk factor for stress-induced eating and obesity.

Long-lasting memories that associate environmental stimuli with the effects of alcohol are known to be a main cause of relapse and are a major challenge in the treatment of alcohol addiction. It is reasonable to hypothesize that disrupting consolidated alcohol-related memories might help to prevent relapses. The reconsolidation theory states that a consolidated memory could again become labile and susceptible to disruption by protein synthesis inhibition or NMDA-antagonism after memory retrieval. This has been shown for cocaine- and morphine-associated memories in several recent studies. The aim of our investigations was to examine in an animal model for cue-induced relapse to alcohol-seeking behavior whether the behavioral impact of previously conditioned alcohol associated cues is significantly reduced by blocking the reconsolidation of learned alcohol associations. We show that reconsolidation of alcohol memories is disrupted by post-retrieval ICV-administration of the protein synthesis inhibitor anisomycin. Similarly, post-retrieval i.p.-administration of the NMDA antagonist MK-801 reduced alcohol seeking behavior during the following test day as compared to vehicle treated rats. Pharmacological disruption of reconsolidation of alcohol-associated memories may thus provide a potential therapeutic strategy for the prevention of relapse in alcohol addiction.

In humans alcohol seeking behavior is frequently evoked by the retrieval of memories associated with an alcohol experience. Consolidated memories can become labile if reactivated by reexposure. The aim of our study was to examine whether the behavioral impact of previously conditioned alcohol associated cues is significantly reduced by blocking the reconsolidation of the previously learned alcohol associations that are retrieved by reexposition. For this purpose we applied an animal model for cue-induced relapse to alcohol-seeking behavior. We show that post-retrieval i.p.-administration of 0.1 mg/kg of the NMDA antagonist MK-801 (n=8-10 per group) significantly reduced alcohol seeking behavior during the following test day as compared to vehicle treated animals. Similarly, memory reconsolidation was disrupted by ICV administration of 400 μg of the protein synthesis inhibitor anisomycin (n=9-11 per group). Pharmacological disruption of reconsolidation of alcohol-associated memories may thus provide a potential therapeutic strategy for the prevention of relapse in alcohol addiction.

Quantum theory is a powerful framework for probabilistic modeling of cognition. Strong empirical evidence suggests the context- and order-dependent representation of human judgment and decision-making processes, which falls beyond the scope of classical Bayesian probability theories. However, considering behavior as the output of underlying neurobiological processes, a fundamental question remains unanswered: Is cognition a probabilistic process at all?