Opposing regulation of pair bond formation by cAMP signaling within the nucleus accumbens shell

Abstract

The formation of monogamous pair bonds, by prairie voles, is facilitated by activation of dopamine (DA) D2-like, but not D1-like, receptors within the nucleus accumbens (NAcc) shell. Because DA exerts opposing regulation of cAMP production depending on the subtype of receptor activated, we tested the hypothesis that DA regulation of pair bond formation is mediated via the cAMP signaling cascade. Consistent with activation of D2-like receptors, decreasing cAMP signaling, by blocking cAMP binding sites on protein kinase A (PKA), facilitated partner preference formation. Conversely, increasing cAMP signaling, by preventing the activation of inhibitory G-proteins, activating stimulatory G-proteins, or stimulating PKA prevented the formation of mating-induced partner preferences. These manipulations were effective in the shell, but not the core, of the NAcc. Together, these data demonstrate opposing regulation over pair bond formation by cAMP signaling within the NAcc shell.

Figure 1.

Locations of site-specific drug infusions. a, Infusions for drug induced facilitation of partner preferences into either the NAcc shell or core. b, Infusions for pharmacological blockade of mating-induced partner preferences focused on the NAcc shell.

Figure 2.

Decreased PKA activity within the NAcc shell, but not core, facilitates partner preferences. Infusions of CSF (n = 8) resulted in nonselective side-by-side contact between partners and strangers. Intra-shell (n = 8), but not core (n = 8) administration of Rp (8 ng) induced a significant partner preference. Activation of PKA with Sp (8 ng) did not induce partner preferences when infused in either the shell (n = 8) or the core (n = 7). *p < 0.05, significantly more time with the partners compared with strangers. Error bars indicate SEM.

Figure 3.

Increased cAMP signaling within the NAcc shell blocks mating-induced partner preferences. Subjects receiving control infusions of CSF (n = 4) showed robust mating-induced partner preferences. Preventing activity of inhibitory G-proteins with PTX (20 ng; n = 8), activating stimulatory G-proteins with CTX (20 ng; n = 8), and activating PKA with Sp (8 ng; n = 7) prevented mating-induced partner preferences. Decreasing PKA activity with Rp (8 ng; n = 6) did not alter mating-induced partner preferences. *p < 0.05, significantly more time with the partners compared with strangers. Error bars indicate SEM.