Inhibition of vasopressin V1a receptors in the medioventral bed nucleus of the stria terminalis has sex- and context-specific anxiogenic effects

Duque-Wilckens, Natalia; Steinman, Michael Q.; Laredo, Sarah A.; Hao, Rebecca; Perkeybile, Allison M.; Bales, Karen L.; Trainor, Brian C.

doi:10.1016/j.neuropharm.2016.07.018

Cited by 45 publications

(87 citation statements)

References 57 publications

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“…**p < 0.01 vs. aCSF, ***p < 0.001 vs. aCSF, † † p < 0.01 vs. OTA. Group N's: female/OTA: 7, male/OTA: 8, female/ aCSF: 7, male/aCSF: 10, female/miss: 7, male/miss: 13. no effect on social approach or locomotor behavior in female California mice [56]. In addition, although L-368,899 has the ability to act as an antagonist at vasopressin receptor 1B (V1bR) [57], levels of V1bR have been reported to be either very low or nonexistent in the NAc of male rats [58][59][60], therefore we do not expect our findings to be a result of V1bR antagonism.…”

Section: Discussionmentioning

confidence: 72%

Social approach and social vigilance are differentially regulated by oxytocin receptors in the nucleus accumbens

Williams

Duque-Wilckens

Ramos-Maciel

et al. 2020

Neuropsychopharmacol.

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Oxytocin is currently being considered as a novel therapeutic for anxiety disorders due to its ability to promote affiliative behaviors. In the nucleus accumbens (NAc) activation of oxytocin receptors (OTR) promotes social approach (time spent near an unfamiliar individual). Here, we show that stressful social experiences reduce the expression of NAc OTR mRNA, coinciding with decreases in social approach. Social stressors also increase social vigilance, characterized as orienting to an unfamiliar individual without approaching. Vigilance is a key component of behavioral inhibition, a personality trait that is a risk factor for anxiety disorders. To understand whether NAc OTR can modulate both social approach and vigilance, we use pharmacological approaches to assess the impact of activation or inhibition of NAc OTR downstream pathways on these behaviors. First, we show that in unstressed male and female California mice, inhibition of OTR by an unbiased antagonist (L-368,899) reduces social approach but does not induce social vigilance. Next, we show that infusion of Atosiban, an OTR-Gq antagonist/OTR-Gi agonist, has the same effect in unstressed females. Finally, we show that Carbetocin, a biased OTR-Gq agonist, increases social approach in stressed females while simultaneously inhibiting social vigilance. Taken together these data suggest that OTR in the NAc differentially modulate social approach and social vigilance, primarily through an OTR-Gq mechanism. Importantly, pharmacological inhibition of OTR alone is insufficient to induce vigilance in unstressed mice, suggesting that mechanisms modulating social approach may be distinct from mechanisms modulating social vigilance.

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Section: Discussionmentioning

confidence: 72%

Social approach and social vigilance are differentially regulated by oxytocin receptors in the nucleus accumbens

Williams

Duque-Wilckens

Ramos-Maciel

et al. 2020

Neuropsychopharmacol.

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“…Finally, the social behavior of AIE exposed males was insensitive to pharmacological blockade of endogenous activity at V1a-Rs, whereas SR-49059 decreased social investigation and dose-dependently altered play fighting in water-exposed control males, suggesting that V1a-Rs may be involved in modulation of the effects of AVP on social behavior under normal circumstances (see Duque-Wilckens et al 2016). The lack of effects of the V1a-R antagonist on social behavior in ethanol-exposed males is in accordance with the results of Exp.…”

Section: Discussionmentioning

confidence: 97%

Oxytocin and vasopressin modulation of social anxiety following adolescent intermittent ethanol exposure

et al. 2018

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These findings demonstrate that AIE induces changes in OXT-R and AVP-R surface expression in the hypothalamus along with social anxiety-like alterations in male rats. These social anxiety-like alterations can be reversed either by activation of the OXT system or by suppression of the AVP system, data that support the hypothesis that social anxiety-like alterations induced by adolescent alcohol exposure in male rats are associated at least in part with an OXT/AVP imbalance.

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“…As mentioned above, this brain area is located at the intersection of several key circuits underlying social and mood-related behaviors and involving OT and AVP neuropeptides. For instance, infusions of the V1a receptor antagonist into the medioventral BNST of California mice induced www.nature.com/scientificreports www.nature.com/scientificreports/ anxiogenic effects in social and nonsocial contexts 37 . Blocking the OT receptor in the dorsolateral BNST reduced the acquisition of conditioned cued fear, but left the baseline startle and non-cued fear (background anxiety) intact 38 .…”

Section: Discussionmentioning

confidence: 99%

Effects of neural estrogen receptor beta deletion on social and mood-related behaviors and underlying mechanisms in male mice

Dombret

Naulé

Trouillet

et al. 2020

Sci Rep

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Estradiol derived from neural aromatization of testosterone plays a key role in the organization and activation of neural structures underlying male behaviors. This study evaluated the contribution of the estrogen receptor (ER) β in estradiol-induced modulation of social and mood-related behaviors by using mice lacking the ERβ gene in the nervous system. Mutant males exhibited reduced social interaction with same-sex congeners and impaired aggressive behavior. They also displayed increased locomotor activity, and reduced or unaffected anxiety-state level in three paradigms. However, when mice were exposed to unescapable stress in the forced swim and tail suspension tests, they spent more time immobile and a reduced time in swimming and climbing. These behavioral alterations were associated with unaffected circadian and restraint stress-induced corticosterone levels, and unchanged number of tryptophan hydroxylase 2-immunoreactive neurons in the dorsal raphe. By contrast, reduced mRNA levels of oxytocin and arginine-vasopressin were observed in the bed nucleus of stria terminalis, whereas no changes were detected in the hypothalamic paraventricular nucleus. The neural ERβ is thus involved to different extent levels in social and mood-related behaviors, with a particular action on oxytocin and arginine-vasopressin signaling pathways of the bed nucleus of stria terminalis, yet the involvement of other brain areas cannot be excluded.aggressive behavior of mutant males can be observed in another behavioral test using a neutral testing cage 14 .Furthermore, yet another study on ERβ knockout males showed no impairment of social recognition memory 15 .Concerning mood-related behaviors, few studies have been conducted in male mice and rats. This either resulted in minor effects induced by global ERβ knockout in mice 16 , or significant changes following chronic administration of selective ERβ agonists or androgen metabolites acting at ERβ on the anxiety state level in rats [17][18][19] . By comparison, more studies are available on female behaviors and these all converge on the role of ERβ in mediating estradiol effects 6,16,[20][21][22][23] . This involves at least in part the maintenance of serotonergic neurons and regulation of the expression of tryptophan hydroxylase (TPH), the key enzyme involved in serotonin synthesis in the dorsal raphe 24 .In this context, the present work was undertaken in order to evaluate in the same study the neural role of ERβ in social and mood-related behaviors using male mice lacking the ERβ gene in the whole nervous system, without interference with peripheral effects of this receptor. For this purpose, control and mutant mice were subjected to behavioral tests that measure social interaction, anxiety-related behavior (elevated O-maze, dark-light box and open field), locomotor activity, despair-like behavior (forced swim and tail suspension tests), sucrose preference test, and aggressive behavior (resident-intruder test). Corticosterone levels were measured under basal circadian and induce...

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Inhibition of vasopressin V1a receptors in the medioventral bed nucleus of the stria terminalis has sex- and context-specific anxiogenic effects

Cited by 45 publications

References 57 publications

Social approach and social vigilance are differentially regulated by oxytocin receptors in the nucleus accumbens

Social approach and social vigilance are differentially regulated by oxytocin receptors in the nucleus accumbens

Oxytocin and vasopressin modulation of social anxiety following adolescent intermittent ethanol exposure

Effects of neural estrogen receptor beta deletion on social and mood-related behaviors and underlying mechanisms in male mice

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