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Differential activation of arginine-vasopressin receptor subtypes in the amygdaloid modulation of anxiety in the rat by arginine-vasopressin

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Abstract

Rationale

The amygdala plays a paramount role in the modulation of anxiety and numerous studies have shown that arginine vasopressin (AVP) elicits anxiogenic effects following either its systemic or septal administration.

Objectives

The aim of this paper was to study the involvement of vasopressinergic neurotransmission in the amygdaloid modulation of unconditioned anxiety and to ascertain whether or not AVP receptor subtypes may have a differential role in this modulation.

Methods

Anxiety behavior was evaluated both in Shock-Probe Burying Test and Light-Dark Box following the bilateral microinfusion of AVP alone or AVP together with either AVP 1a or AVP 1b receptor antagonists into the central amygdala (CeA).

Results

AVP microinfusion elicited at low (1 ng/side) but not at high doses (10 ng/side) anxiogenic-like responses in the Shock-Probe Burying Test but not in the Light-Dark Box. SSR149415, an AVP 1b antagonist unlike Manning compound, an AVP 1a antagonist, fully prevented AVP effects in the Shock-Probe Burying Test when it was administered simultaneously with AVP. In addition, oxytocin receptor blockade also failed to affect AVP effects. No effects of any AVP antagonist by itself were observed in both anxiety paradigms.

Conclusions

Our results indicate that AVP 1b receptor contribute to the amygdaloid modulation of anxiety at least in the context of the Shock-Probe Burying Test since no effects were noticed in the Light-Dark Box. It remains to the future to ascertain whether AVP receptor subtypes have indeed differential actions either in the modulation of global or specific features of unconditioned anxiety.

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Funding

This work was supported by Vetenskapsrådet in year 2015–2017 (No. 348-2014-4396) as an international collaborative research grant from the Swedish Research Council (2015-2017) with Mexico (MPM) and by grants UNAM-DGAPA-PAPIIT IN204314 and IN205217 to MPM, CB-2013/22173 from Consejo Nacional de Ciencia y Tecnología (CONACYT) to MPM, the Swedish Research Council (04X-715) to KF, and by AFA Försäkring (130328) to KF. Oscar René Hernández-Pérez is a doctoral student from Programa de Doctorado en Ciencias Biomédicas, Universidad Nacional Autónoma de México (UNAM) and received scholarship 289977 from CONACYT.

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Author notes

  1. José Anias-Calderón is deceased. This paper is dedicated to his memory.

    • José Anias-Calderón
Authors

Corresponding author

Correspondence to Miguel Perez de la Mora.

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Conflict of interest

The authors declare that they have no conflict of interest.

Electronic supplementary material

Supplementary Fig. 1

Representative coronal section (a) and schematic representation (b) of the sites of cannulae implantation within the left and right amygdala from rats microinjected with saline, arginine-vasopressin (AVP), and AVP1b receptor antagonist and evaluated behaviorally in the Shock-Probe Burying Test and Light-Dark Box. Stereotaxical levels correspond to those of the rat brain atlas of Paxinos and Watson (1986). Because of the high density of cannulae tips in some of the sections, some overlap of the injection sites has been produced. ACo, anterior amygdaloid cortical nucleus; BLA, basolateral amygdaloid nucleus; BMA, amygdaloid basomedial nucleus; CeL, central amygdaloid nucleus, lateral division; CeM, central amygdaloid nucleus, medial division; IM, main intercalated paracapsular island; LA, lateral amygdala; MeA, medial amygdaloid nucleus. (GIF 326 kb)

High resolution (TIFF 5477 kb)

Supplementary Fig. 2

Extent of diffusion of [FITC] [Ahx]CYIQNCPLG[amide] microinfused into the amygdala. [FITC] [Ahx]CYIQNCPLG[amide], a fluorescent oxytocin analog, having a similar molecular weight and amino acid composition as AVP was microinfused into the amygdala under the conditions described in the “Experimental procedures” and its extent of diffusion was evaluated after 10 min following its injection. a A cannula tip is shown within CeA in a coronal section counterstained with Cresyl Violet at a level − 2.56 mm according to the atlas of Paxinos & Watson (1986). b Fluorescence microscopy analysis (×4) indicated that [FITC] [Ahx]CYIQNCPLG[amide] remains in the CeA near the cannulae tip, radially diffusing to occupy the volume of a sphere of 0.38 mm3 from the site of its injection. The fluorescent oxytocin analog is taken up into surrounding nerve cell bodies on the medial, ventral, and lateral side. c Amplification (×10) from the same field. BLA, basolateral amygdaloid nucleus; CeA, central amygdaloid nucleus; MeA, medial amygdaloid nucleus; OXT-FITC, [FITC] [Ahx]CYIQNCPLG[amide]. (JPEG 182 kb)

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Hernández-Pérez, O.R., Crespo-Ramírez, M., Cuza-Ferrer, Y. et al. Differential activation of arginine-vasopressin receptor subtypes in the amygdaloid modulation of anxiety in the rat by arginine-vasopressin. Psychopharmacology 235, 1015–1027 (2018). https://doi.org/10.1007/s00213-017-4817-0

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  • DOI: https://doi.org/10.1007/s00213-017-4817-0

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