Membrane and synaptic effects of corticotropin-releasing factor on periaqueductal gray neurons of the rat

Corticotropin-releasing factor (CRF) has been identified as a major component of the hypothalamic-pituitary-adrenal (HPA) axis. By stimulating the release of adrenocorticotropin hormone (ACTH), CRF acts as a key mediator of the stress response. However, CRF receptors and neuronal elements are present in many extrahypothalamic regions of the brain. A region that contains both CRF-ergic neurons and CRF receptors is the midbrain periaqueductal gray (PAG). The physiological effects of CRF in the PAG are unknown. In this study, an in vitro preparation, extracellular and intracellular patch-clamp recordings, were used to examine the effects of CRF, applied through an injecting electrode, on PAG neurons. Recordings were made from 147 neurons in the PAG. CRF injecting electrode concentrations of 0.05 and 1 muM were tested. At the higher concentration, CRF had a predominant excitatory effect on the neurons, and at the lower concentration, CRF produced no significant effect on the neurons. The excitatory effect was dose dependent and was often associated with a depolarization in membrane potential in intracellular recordings. Application of the CRF antagonist, a-helical CRF, blocked this excitatory effect. It is concluded that CRF has a predominant excitatory effect on PAG neurons. It is also concluded that CRF is not acting presynaptically. This excitatory effect of CRF on PAG neurons may lead to activation of a descending analgesic pathway. (C) 2003 Elsevier B.V. All rights reserved.