Discovered a mechanism by which CRF modulates neuronal activity in drug addiction



It is known that stress is a common cause of relapse and increases addictive behaviours. Corticotropin-releasing factor (CRF), a 41 amino acid peptide, plays an obligatory role in the activation of the hypothalamic-pituitary-adrenal axis and the subsequent release of glucocorticoids in response to stressful events. It is also known that extrahypothalamic CRF mediates many behavioural responses to stress. In the periphery “free” CRF is inactivated by a binding protein (BP), although a high level of CRF-BP has been detected in the Central Nervous System, its exact role is not clear. The CRF action on target cells involves two receptors, CRF-R1 and CRF-R2. The dopaminergic neurons of the ventral tegmental area (VTA) are a CRF-target and play a key role in both acute and chronic responses to addictive drugs. The mechanism by which CRF modulates neuronal activity in circuits involved in drug addiction is poorly understood. Mark A. Ungless and his colleagues (Corticotropin-Releasing Factor Requires CRF Binding Protein to Potentiate NMDA Receptors via CRF Receptor 2 in Dopamine Neurons, Neuron 39, 401-407, 2003) show that CRF induces a potentiation of NMDA receptors in dopamine neurons of the VTA, involving CRF-R2 and CRF-BP. This first evidence for a CRF-R2 and CRF-BP specific role in the modulation of neuronal activity suggests that NMDA receptors in the VTA may be a target for both stress and drug of abuse.


BM&L-October 2003