Vasopressin indirectly excites dorsal raphe serotonin neurons through activation of the vasopressin1A receptor

Abstract

The neuropeptide vasopressin (AVP) 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 dorsal raphe serotonin system.

Sex differences in monoamines following amphetamine and social reward in adolescent rats.

“…Within Amyg, dendritic arborization and glial volume are increased in males relative to females, suggesting a role in the greater play behavior exhibited in males (Cooke, Stokas, & Woolley, 2007). Further, vasopressin microinjection enhances DA utilization and systemic injections of vasopressin increases excitatory postsynaptic currents of 5-HT neurons in Amyg (Rood & Beck, 2014), suggesting a critical interaction between social play-related hormones and monoamine neural systems (van Heuven-Nolsen, de Kloet, De Wied, & Versteeg, 1984). …”

Bisphenol A Exposure During Early Development Induces Sex-Specific Changes in Adult Zebrafish Social Interactions

“…Since agonistic displays may be markedly affected by this interaction, xenoestrogenic activity of BPA as it relates to ER and ERRγ agonism (general: Zuercher et al 2005; Ben-Jonathan and Steinmetz 1998; human: Okada et al 2008; rat: Washington et al 2001), and the consequent effects on the serotonergic system during development may be an example of BPA-induced neuroendocrine disruption. Because serotonin is important during brain development and in controlling levels of aggression, and BPA enhances 5-HT activity, BPA-induced changes in embryonic 5-HT levels may be responsible for altered brain development (fish: Elipot et al 2013; Dahlbom et al 2012; Clotfelter et al 2007; mice: Rood and Beck 2013; rat: Cao et al 2013; Donner and Handa 2011; Matsuda et al 2010; González et al 2008; Honma et al 2006; Orozco-Suárez 2003; Persico et al 2000; Yan et al 1997). …”

Differential effects of oxytocin on mouse hippocampal oscillations in vitro

“…Brain slices were perfused for at least 2 h with desGlyDTyrOVT ‐ ACSF before TGOT or vasopression were added to the solution in a concentration of 10 or 20 n m respectively. As an additional control, we used the most specific vasopressin 1a receptor antagonist [Phenylacetyl1,O‐Me‐D‐Tyr2,Arg6,8,Lys9]‐vasopressin amide (Sigma Aldrich) in a concentration of 300 n m (Rood & Beck, ).…”