No abstract

No abstract

No abstract

Rats with medial prefrontal cortex (mPFC) lesions are impaired in attentional set-shifting, when it is required to shift to a previously irrelevant perceptual dimension. The main source of noradrenergic input to the mPFC is from the locus coeruleus via the dorsal noradrenergic ascending bundle (DNAB). This study examined the effects of selective cortical noradrenaline depletion following 6-hydroxydopamine-induced lesions of the DNAB on attentional set-shifting and other aspects of discrimination learning and performance. Rats learned to dig in baited bowls, and then acquired discriminations based on one of two aspects of a bowl--odour or digging medium. The task tested acquisition of novel discriminations (both intra- and extra-dimensional) and reversal learning when contingencies were reversed with the same stimuli. At the conclusion of testing, the DNAB-lesioned rats were shown to have a selective depletion of noradrenaline of approximately 70% within the mPFC (cingulate and prelimbic cortex subregions), with no other significant changes in dopamine or 5-hydroxytryptamine. Rats required more trials to learn new discriminations when attentional shifting was required [extra-dimensional (ED)-shift]. Rats with dorsal noradrenergic ascending bundle (DNAB) lesions were impaired in novel acquisitions when an ED-shift was required, but were unimpaired in reversal learning and other aspects of discrimination learning, relative to controls. These data are consistent with other evidence implicating noradrenaline (NA) in attentional set-shifting, and contrast with effects of manipulations of 5-hydroxytryptamine (5-HT) and acetylcholine within the medial prefrontal cortex (mPFC). The findings are also relevant to recent theorizing about the functions of the coeruleo-cortical noradrenergic system.

There is recognition that biomedical research into the causes of mental disorders and their treatment needs to adopt new approaches to research. Novel biomedical techniques have advanced our understanding of how the brain develops and is shaped by behaviour and environment. This has led to the advent of stratified medicine, which translates advances in basic research by targeting aetiological mechanisms underlying mental disorder. The resulting increase in diagnostic precision and targeted treatments may provide a window of opportunity to address the large public health burden, and individual suffering associated with mental disorders. While mental health and mental disorders have significant representation in the "health, demographic change and wellbeing" challenge identified in Horizon 2020, the framework programme for research and innovation of the European Commission (2014-2020), and in national funding agencies, clear advice on a potential strategy for mental health research investment is needed. The development of such a strategy is supported by the EC-funded "Roadmap for Mental Health Research" (ROAMER) which will provide recommendations for a European mental health research strategy integrating the areas of biomedicine, psychology, public health well being, research integration and structuring, and stakeholder participation. Leading experts on biomedical research on mental disorders have provided an assessment of the state of the art in core psychopathological domains, including arousal and stress regulation, affect, cognition social processes, comorbidity and pharmacotherapy. They have identified major advances and promising methods and pointed out gaps to be addressed in order to achieve the promise of a stratified medicine for mental disorders.