Dopaminergic Regulation of Pair Bonding in the Socially Monogamous Prairie Vole

• Main Author: Nevárez, Natalie
• Format: Dissertation
• Language: English
• Published: ProQuest Dissertations & Theses 01-01-2017
• Subjects: Neurosciences; Pharmacology
• ISBN: 9780355656688; 035565668X

The development and maintenance of pair bonds in the socially monogamous prairie vole is regulated in part by the mesolimbic dopamine system. My dissertation work investigates dopamine signaling mechanisms involved in the development of these selective social attachments, the adaptations of this system in the maintenance of such bonds, and finally, how oxytocin may interact with dopamine in these processes. I first replicate findings showing that the mixed D2/D3 receptor agonist, quinpirole when infused into the nucleus accumbens shell, induces robust partner preferences. I subsequently sought to determine if selective activation of D2 or D3 receptors within the this region, via infusions of the specific D2R agonist 5,6,7,8-Tetrahydro-6-(2-propenyl)-4H-thiazolo[4,5-d]azepine-2-amine dihydrochloride (B-HT 920) or the specific D3R agonist R(+)-2-Dipropylamino-7-hydroxy-1,2,3,4-tetrahydronaphthalene hydrobromide (7-OH-DPAT), influenced partner preference formation. Partner preference testing showed that selective activation of D3 receptors is sufficient to induce partner preferences while D2 receptor activation is not. In a second set of experiments I utilized these same drugs in combination with fast scan cyclic voltammetry to measure DA release inhibition via autoreceptors in the striatum. B-HT 920 had highest effect in the dorsal striatum whereas quinpirole was more effective in the nucleus accumbens shell at inhibiting dopamine release than either the selective D2 or D3 agonist. Surprisingly, 7-OH-DPAT, showed similar effects in both regions examined. This result was unanticipated as inhibition of dopamine release by agonists is thought to reflect receptor distribution and reports in other species show greater density D3 receptors in the nucleus accumbens shell compared with dorsal striatum. Our results suggest that the prairie vole shows a unique response to quinpirole compared to other species or that the distribution of D3 receptors in the prairie vole may not follow the same pattern as other species. In a final set of experiments, I utilized fast scan cyclic voltammetry to measure dopamine release dynamics in the nucleus accumbens shell of sexually naïve and 28-day pair bonded prairie voles. We demonstrate that pregnancy status is reflected in dopamine release in males after 28 days of pairing such that males from pairs that became pregnant quickly after pairing show the largest increases. Additionally, we test the effects of the dopamine D2/D3 receptor agonist, quinpirole, on electrically stimulated dopamine release in the dorsal striatum and nucleus accumbens as a measure of dopamine autoreceptor functionality. Interestingly, dose response curves to treatment with quinpirole showed that pair bonded prairie voles show subsensitive dopamine autoreceptor activity. In a final experiment, we show that increased oxytocin tone can mimic this effect of pair bonding at the dopamine autoreceptor in sexually naïve animals. Together, these data provide support for an essential role for the DA D3 receptor subtype in regulating the development of social attachments in male prairie voles. Additionally, these data show a long-term adaptation in DA signaling in pair bonded prairie voles, which is both sex-specific and fecundity-dependent. Finally, I show that oxytocin facilitates this neuroadaptation in prairie voles that have not yet been pair bonded. These data represent an important advance for the field since these signaling mechanisms may be valid therapeutic targets to treat social deficits in humans. Taken together, these research findings have provided valuable insight into the role of the DA and oxytocin systems in affiliative behavior and also have broad implications for our understanding of social bonding as a motivated behavior.