Glucocorticoid receptor involvement in pair bonding in female prairie voles: The effects of acute blockade and interactions with central dopamine reward systems

doi:10.1016/j.neuroscience.2005.04.012

Neuroscience

Volume 134, Issue 2, 2005, Pages 369-376

https://doi.org/10.1016/j.neuroscience.2005.04.012 Get rights and content

Abstract

Induction of partner preferences in monogamous prairie voles (Microtus ochrogaster) was used to examine the possibility that blockade of glucocorticoid receptors may be rewarding in females of this species. We first examined the ability of either a mineralocorticoid receptor antagonist (spironolactone) or a glucocorticoid receptor antagonist (RU-486) to induce partner preferences in females. Peripheral administration of either of the antagonists was capable of inducing partner preferences, although the effective dose for RU-486 was an order of magnitude lower than that for spironolactone. We then examined a potential interaction of glucocorticoid receptor with central dopamine in pair bonding by treating females with i.c.v. dopamine receptor antagonists (haloperidol, SCH23390, or eticlopride) prior to peripheral administration of RU-486. All of the dopamine antagonists were capable of reversing the effects of glucocorticoid receptor blockade on pair bonding. These results establish the ability for acute blockade of glucocorticoid to induce pair bonds in female voles. Further, this effect appears to be mediated via an interaction with central dopamine systems. Together these findings support the possibility that, unlike other model systems, reductions in glucocorticoid receptor activity may enhance reward in female prairie voles.

Section snippets

Experimental procedures

All procedures followed accepted animal care and use guidelines and were approved by the Institutional Animal Care and Use Committee at Florida State University. Care was taken to minimize the number of animals used and to minimize discomfort. All drugs were purchased from Sigma-Aldritch, St. Louis, MO, USA.

Subjects were female offspring of the F4 generation of a laboratory colony of prairie voles (Microtus ochrogaster) originating from Illinois. After weaning at about 21 days of age, pups were

Results

As mentioned, all groups that received i.p. injections of sesame oil displayed partner preferences regardless of whether RU-486 was present or not (Table 1). Replacing sesame oil with propylene glycol as an injection vehicle eliminated this confound (Fig. 1).

Both spironolactone and RU-486 were capable of affecting partner preferences in female prairie voles (Fig. 1). As expected vehicle treatment did not produce partner preferences after 6 h of non-sexual cohabitation (t=0.54, P=0.61). Blockade

Results

As expected from the results of experiment 1, 4.0mg/kg of RU-486 induced partner preferences when paired with i.c.v. administration of vehicle (t=3.41, P<0.01; Fig. 2). When RU-486 treatment was paired with central administration of haloperidol, females spent equal amounts of time with stranger as with the partner (t=0.85, P=0.42). We then examined the potential roles of dopamine receptor sub-types in GR-blockade-induced pair bonding. Treating females with SCH23390, a D₁ sub-type dopamine

Discussion

Stress can significantly impact pair bond formation in monogamous voles (DeVries et al., 1996), presumably via changes in circulating levels of corticosterone. In female prairie voles, stress and the associated increases in corticosterone inhibit the formation of pair bonds (DeVries et al., 1995, DeVries et al., 1996) whereas adrenalectomy facilitates pair bond formation (DeVries et al., 1995). Moreover, upon exposure to a male, sexually naïve prairie vole females experience a significant

Acknowledgments

We thank Mr. Michael Smeltzer, Mr. Kyle Gobrogge, and Dr. Kathleen Curtis for helpful suggestions. This work was supported by National Institutes of Health grants NICHD 40722 (J.T.C.) and NIMH 58616 and NIMH 66734 (Z.W.).

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Monogamous pair bonding has evolved to enhance reproductive success and ensure offspring survival. Although the behavioral and neural mechanisms regulating the formation of pair bonds have been relatively well outlined, how these relationships are regulated and maintained across the lifetime of an individual remains relatively unexplored. One way to explore this is to study the maintenance of a social bond across a major life-history transition. The transition to motherhood is among the most poignant moments in the life history of a female, and is associated with significant neural and behavioral changes and shifting priorities. The nucleus accumbens (NAc) is known to modulate social valence and is central to mammalian pair bonding. In this study, we investigated two mechanisms driving variation in bond strength in the socially monogamous prairie vole (Microtus ochrogaster). We manipulated neural activity of the NAc at two distinct stages of life-history, before and after the birth of offspring, to assess how neural activity and social contexts modulate female pair bond strength. Our results showed DREADD (Designer Receptor Exclusively Activated by Designer Drugs) inhibition of the NAc decreases affiliative behavior towards the mating partner, whereas DREADD activation of the NAc increases affiliative behavior of strangers, thereby decreasing social selectivity. We also found a robust “birth effect” on pair bond strength, such that bonds with partners were weakened after the birth of offspring, an effect not attributable to the amount of cohabitation time with a partner. Overall, our data support the hypotheses that NAc activity modulates reward/saliency within the social brain in different ways, and that motherhood comes with a cost for the bond strength between mating partners.
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As there are few studies that include an uninjected control group, many vehicle effects may be overlooked, particularly if a vehicle other than physiological saline is employed. The few studies to use an uninjected control group or to directly examine the effects of sesame oil have found effects with different modes of administration (PO, IP, SC; Anton et al., 1974; Curtis and Wang, 2005; Colafranceschi et al., 2007; Clipperton-Allen et al., 2010) and in various species. Sesame oil is known to have metabolic effects, although in the case of the current study, it seems unlikely that these effects would persist 48 h after administration.
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Behavioural neuroscienceGlucocorticoid receptor involvement in pair bonding in female prairie voles: The effects of acute blockade and interactions with central dopamine reward systems

Abstract

Section snippets

Experimental procedures

Results

Results

Discussion

Acknowledgments

Neuroscience

Physiol Behav

Physiol Behav

Physiol Behav

Brain Res

Psychoneuroendocrinology

Brain Res

Brain Res

Physiol Behav

Neuroscience

Neuroscience

Pharmacol Biochem Behav

Physiol Behav

Am J Surg

Brain Res

II. Patterns of estrus termination following vaginocervical stimulation. Horm Behav

Neuron

Pharmacol Biochem Behav

Gen Comp Endocrinol

Brain Res

Brain Res

Horm Behav

Toxicology

Horm Behav

Differential effect of stress on in vivo dopamine release in striatum, nucleus accumbens, and medial frontal cortex

J Neurochem

Type I corticosteroid receptor-like immunoreactivity in the rat CNS: distribution and regulation by corticosteroids

J Comp Neurol

A critical role for nucleus accumbens dopamine in partner-preference formation in male prairie voles

J Neurosci

Chronic estrogen-induced alterations in adrenocorticotropin and corticosterone secretion, and glucocorticoid receptor-mediated functions in female rats

Endocrinology

Adrenocorticoid hormones and the development and expression of mammalian monogamy

Ann N Y Acad Sci

Behavioural neuroscience
Glucocorticoid receptor involvement in pair bonding in female prairie voles: The effects of acute blockade and interactions with central dopamine reward systems