Limbic circuit connectivity and the stress response: New insights into the mammalian nociceptin peptide system

Considerable progress has been made in understanding the neurobehavioral effects of nociceptin peptide (N/OFQ) and its NOP receptor. Recent interest has focused on its role in stress and cognition, with consideration of therapeutic potential in regard to anxiety and mood disorders. Research has interrogated the mechanisms of action of N/OFQ peptide in the context of stress-related behavior. We are interested in the endogenous role of N/OFQ and NOP receptor in terms of adaptation to chronic stress. Our research has highlighted the importance of associated limbic regions including the bed nucleus, extended amygdala, in addition to thalamic reticular nucleus as important sites for long-term adaptations in endogenous N/OFQ function in chronic stress. Such research raises interest in appreciation of extended limbic connections and novel pathways which allow us to reevaluate current understanding of stress neurocircuitry. Examination of endogenous N/OFQ-NOP receptor modulation of monoaminergic and amino acid transmitter systems in this extended limbic architecture will facilitate deeper understanding of the tonic control of behavior. Application of in vivo experimental approaches to models of abnormal neurodevelopment and heightened stress vulnerability in adulthood will enable the role of N/OFQ in complex neuropsychiatric disorders including schizophrenia and post-traumatic stress disorder to be defined.