Delta opioid receptors: a new target for antidepressants.

Depression is a major contributor to global disability. However, treatments are ineffective, resulting in the need for new therapies. My lab has discovered that in the mouse hippocampus the pro-cognitive atypical antidepressant tianeptine employs a novel form of receptor crosstalk, whereby it activates postsynaptic -opioid receptors ( -OR) causing an enhancement of glutamatergic excitation. Additionally, this antidepressant activates presynaptic opioid receptors to decrease the release of the inhibitory neurotransmitter GABA to cause neuronal disinhibition. Using behavioural and electrophysiological techniques the project will investigate how this synergistic enhancement of excitation and impaired inhibition may underpin the antidepressant and pro-cognitive actions of tianeptine. Dysregulation of endogenous opioid peptide levels is implicated in mood disorders. Therefore, the study will be extended to explore whether endogenous opioid peptides e.g. enkephalin might physiologically engage these pre- and post-synaptic opioid receptors to influence mood and cognition. Project provides training in Interdisciplinary Skills and Whole Organism Physiology.