D2 antagonist during development decreases anxiety and infanticidal behavior in adult female prairie voles (Microtus ochrogaster)

Abstract

On postnatal day eight, prairie vole pups were randomly assigned a treatment of 1 mg/kg SKF38393 (D1 agonist), quinpirole (D2 agonist), SCH23390 (D1 antagonist), eticlopride (D2 antagonist), or saline vehicle. As adults, females treated with eticlopride exhibited reduced anxiety-like behavior in an elevated plus maze and a reduction in infanticidal behavior. These behavioral effects were not seen in males. These data demonstrate that a single exposure to a D2 antagonist during development can have persistent, sex-specific effects on behavior into adulthood.Keywords prairie vole; anxiety; alloparenting; dopamine Prairie voles (Microtus ochrogaster) are microtine rodents that are characterized by affiliative social behaviors including selective partner preferences, biparental care, and cooperative breeding [15]. The early endocrine and neuroendocrine environments play a critical role in the development of these species-specific behaviors. A number of hormones that play a key role in the expression of adult prairie vole social behavior have also been shown to play a developmental role as well (corticosterone: [30]; testosterone: [30]; oxytocin: [5][6][7][8]14,29] arginine vasopressin: [37]).Recently dopamine has emerged as a key neurotransmitter in the regulation of prairie vole pair-bonding [3,4,17,23,39]. Prairie voles have been shown to be developmentally sensitive to early exposure to amphetamine, a dopamine reuptake inhibitor [28]. Daily administration of amphetamine over PND 13-15 changed social affiliation levels in adult prairie voles. Both male and female subjects given high doses of amphetamine spent more time alone than saline controls. However, low dose exposed animals showed sexually dimorphic responses to treatment when compared to controls: males spent more time alone, whereas females spent more time affiliating with the stranger. These data indicate that the developing Please send correspondence to: Caroline M. Hostetler, Dept. of Psychology, One Shields Ave., University of California, Davis, CA 95616. Phone: 530-220-3142, Fax: 530-752-2087, chostetler@ucdavis.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. We therefore hypothesized that alterations in dopamine receptor activity at PND8 may have potential long-term effects on behavior. Given that dopamine has been associated with anxiety-related behaviors and maternal behavior in a number of other previously studied species, we also hypothesized that behavior in an elevated plus maze and alloparental responsiveness in prairie voles are influenced by dopaminergic activity. This study was designed...

Genetics of Aggression in Voles

“…6.3F; Aragona et al , 2006). In other work, both brief and extended cohabitation with unfamiliar conspecifics in female prairie voles significantly increased the number of DA-ergic cells in the BNST and MeA (Cavanaugh and Lonstein, 2010) and blocking D2Rs, during development, decreased aggression-related behavior including infanticide in adult female, but not male, prairie voles (Hostetler et al , 2010). Further, pair bonded male prairie voles—displaying aggression toward either male or female intruders, had a significantly higher density of cells in the AH that were double-labeled for tyrosine hydroxylase-ir (TH—rate-limiting enzyme in DA biosynthesis) and Fos-ir than males not exposed to a social stimulus or males that were re-exposed to their familiar female partner (Fig.…”

Neonatal exposure to the D1 agonist SKF38393 inhibits pair bonding in the adult prairie vole

“…Previous research from our lab has found that infanticidal and anxiety-like behaviors are reduced in females neonatally exposed to the D2 antagonist eticlopride (Hostetler et al, 2010). There has been no study of developmental alterations of dopaminergic systems on either partner preference formation or adult-directed aggression in prairie voles.…”

“…Male and female pups were randomly assigned one of the following treatments: saline (vehicle control), or 1 mg/kg SKF38393 (D1 agonist), quinpirole (D2 agonist), SCH23390 (D1 antagonist), or eticlopride (D2 antagonist) in 25μl volume. Age of treatment, drugs, and dosage were based on previous work with prairie voles and neonatal rodent studies (as described in Hostetler et al ., 2010). On postnatal day (P)8, pups were removed from their parents and treatment was administered i.p.…”

“…As adults, all subjects received an elevated plus maze and alloparental care test (as reported in Hostetler et al, 2010), and a juvenile affiliation test (data not shown). At approximately P80, each subject was given a intrasexual aggression test, a partner preference test, and second intrasexual aggression test on three consecutive days.…”

Sex, Drugs, and Violence: Neuromodulation of Attachment and Conflict in Voles

“…In other work, both brief and extended cohabitation with unfamiliar conspecifics in female prairie voles significantly increased the number of DA-ergic cells in the BNST and MeA (Cavanaugh and Lonstein 2010), and blocking D2Rs during development decreased aggression-related behavior including infanticide in adult female, but not male, prairie voles (Hostetler et al 2010). Furthermore, pairbonded male prairie voles that displayed aggression toward either male or female intruders had a significantly higher density of cells in the AH that were doublelabeled for tyrosine hydroxylase (TH, the rate limiting enzyme in DA biosynthesis)-ir and Fos-ir than males not exposed to a social stimulus or males that were re-exposed to their familiar female partner (Figs.…”