title: Vasopressin indirectly excites dorsal raphe serotonin neurons through activation of the vasopressin1A receptor.
abstract: The neuropeptide vasopressin (AVP; arginine-vasopressin) is produced in a handful of brain nuclei located in the hypothalamus and extended amygdala and is released both peripherally as a hormone and within the central nervous system as a neurotransmitter. Central projections have been associated with a number of functions including regulation of physiological homeostasis, control of circadian rhythms, and modulation of social behavior. The AVP neurons located in the bed nucleus of the stria terminalis and medial amygdala (i.e., extended amygdala) in particular have been associated with affiliative social behavior in multiple species. It was recently demonstrated that in the mouse AVP projections emanating from extended amygdala neurons innervate a number of forebrain and midbrain brain regions including the dorsal raphe nucleus (DR), the site of origin of most forebrain-projecting serotonin neurons. Based on the presence of AVP fibers in the DR, we hypothesized that AVP would alter the physiology of serotonin neurons via AVP 1A receptor (V1AR) activation. Using whole-cell electrophysiology techniques, we found that AVP increased the frequency and amplitude of excitatory post-synaptic currents (EPSCs) in serotonin neurons of male mice. The indirect stimulation of serotonin neurons was AMPA/kainate receptor dependent and blocked by the sodium channel blocker tetrodotoxin, suggesting an effect of AVP on glutamate neurons. Further, the increase in EPSC frequency induced by AVP was blocked by selective V1AR antagonists. Our data suggest that AVP had an excitatory influence on serotonin neurons. This work highlights a new target (i.e., V1AR) for manipulating serotonin neuron excitability. In light of our data, we propose that some of the diverse effects of AVP on physiology and behavior, including social behavior, may be due to activation of the DR serotonin system.
authors.affiliation: Department of Anesthesiology and Critical Care, Children's Hospital of Philadelphia, Philadelphia, PA 19104, United States. Electronic address: roodb@email.chop.edu.
authors.forename: B D
authors.initials: BD
authors.lastname: Rood
authors.affiliation: Department of Anesthesiology and Critical Care, Children's Hospital of Philadelphia, Philadelphia, PA 19104, United States; Department of Anesthesiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, United States. Electronic address: becks@email.chop.edu.
authors.forename: S G
authors.initials: SG
authors.lastname: Beck
mesh_terms: D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D011903:Raphe Nuclei / Q000187:drug effects / Q000502:physiology*; D017483:Receptors, Vasopressin / Q000187:drug effects / Q000378:metabolism*; D059326:Serotonergic Neurons / Q000187:drug effects / Q000502:physiology*; D055366:Synaptic Potentials / Q000187:drug effects
chemical_list: D017483:Receptors, Vasopressin; D001127:Arginine Vasopressin
keywords: 6,7-dinitroquinoxaline-2,3-dione; AHP; ANOVA; AP; AVP; BNST; BSA; DIC; DNQX; DR; EGTA; EPSC; HEPES; IPSC; Ir; PB; PBS; PBS with Triton X-100; PBST; TPH; TTX; V(1A)R; V1A receptor; YFP; aCSF; action potential; after-hyperpolarization; analysis of variance; arginine-vasopressin; artificial cerebrospinal fluid; bed nucleus of the stria terminalis; bovine serum albumin; differential interference contrast; dm; dorsal raphe; dorsomedial; electrophysiology; ethylene glycol tetraacetic acid; excitatory post-synaptic current; glutamate; hydroxyethyl piperazineethanesulfonic acid; immunoreactive/immunoreactivity; inhibitory post-synaptic current; phosphate buffer; phosphate buffered saline; serotonin; tetrodotoxin; tryptophan hydroxylase; vasopressin; vasopressin1A receptor; ventromedial; vm; yellow fluorescent protein