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Addictive drugs hijack mechanisms of learning and memory that normally underlie reinforcement of natural rewards and induce synaptic plasticity of glutamatergic transmission in the mesolimbic dopamine (DA) system. In the ventral tegmental area (VTA), a single exposure to cocaine efficiently triggers NMDA receptor-dependent synaptic plasticity in DA neurons,(More)
Cocaine strengthens excitatory synapses onto midbrain dopamine neurons through the synaptic delivery of GluR1-containing AMPA receptors. This cocaine-evoked plasticity depends on NMDA receptor activation, but its behavioral significance in the context of addiction remains elusive. Here, we generated mice lacking the GluR1, GluR2, or NR1 receptor subunits(More)
A fundamental function of the brain is to evaluate the emotional and motivational significance of stimuli and to adapt behaviour accordingly. The IMAGEN study is the first multicentre genetic-neuroimaging study aimed at identifying the genetic and neurobiological basis of individual variability in impulsivity, reinforcer sensitivity and emotional(More)
Negative cognitive bias-the tendency to interpret ambiguous situations pessimistically-is a central feature of stress-related disorders such as depression. The underlying neurobiology of this bias, however, remains unclear, not least because of a lack of translational tools. We established a new ambiguous-cue interpretation paradigm and, with respect to the(More)
A key deficit in alcohol dependence is disrupted prefrontal function leading to excessive alcohol seeking, but the molecular events underlying the emergence of addictive responses remain unknown. Here we show by convergent transcriptome analysis that the pyramidal neurons of the infralimbic cortex are particularly vulnerable for the long-term effects of(More)
The mesolimbic dopaminergic system has been implicated in mediating the motivational effects of opioids and other drugs of abuse. The site of action of opioids within this system and the role of endogenous opioid peptides in modulating dopamine activity therein remain unknown. Employing the technique of in vivo microdialysis and the administration of highly(More)
Despite the generally held view that alcohol is an unspecific pharmacological agent, recent molecular pharmacology studies demonstrated that alcohol has only a few known primary targets. These are the NMDA, GABA(A), glycine, 5-hydroxytryptamine 3 (serotonin) and nicotinic ACh receptors as well as L-type Ca(2+) channels and G-protein-activated inwardly(More)
Mesolimbic dopaminergic neurons are thought to serve as a final common neural pathway for mediating reinforcement processes. However, several recent findings have challenged the view that mesolimbic dopamine has a crucial role in the maintenance of reinforcement processes, or the subjective rewarding actions of natural rewards and drugs of abuse. Instead,(More)
In order to develop a model for a depression-like syndrome in mice, we subjected male C57BL/6 mice to a 4-week-long chronic stress procedure, consisting of rat exposure, restraint stress, and tail suspension. This protocol resulted in a strong decrease in sucrose preference, a putative indicator of anhedonia in rodents. Interestingly, predisposition for(More)
Corticotropin-releasing hormone (CRH) is a potent mediator of endocrine, autonomic, behavioural and immune responses to stress, and has been implicated in the stress-like and other aversive consequences of drug abuse, such as withdrawal from alcohol. Two CRH receptors, Crhr1 and Crhr2, have been identified in the mouse. Crhr1 is highly expressed in the(More)