1. GLUCOCORTICOID RECEPTOR INVOLVEMENT IN PAIR BONDING IN FEMALE PRAIRIE VOLES: THE EFFECTS OF ACUTE BLOCKADE AND INTERACTIONS WITH CENTRAL DOPAMINE REWARD SYSTEMS Curtis, JT and Wang, Z. Neuroscience, 2005. Presented by: Yvonne Pao October 31, 2008

2. REWARD PROCESSING AND PAIR BOND FORMATION Insel, TR 2003

3. PAIR BONDING IN PRAIRIE VOLES

4. NEUROCHEMICALS IN PAIR BONDING Similar FunctionsSexually Dimorphic Functions Dopamine Vasopressin Oxytocin Corticosterone Corticosterone: adrenal stress hormone; activates glucocorticoid receptors (GR) ▫Thought to enhance reward value Opposing effects in males and females: ▫Adrenalectomy in females  enhancement of pair bond formation ▫Adrenalectomy in males  inhibition of pair bond formation Is decreased GR activation rewarding in females?

5. EXPERIMENT 1 Reduce glucocorticoid receptor activation in female prairie voles via injection Pair female with male for 6 hr non-sexual habitation Test females for partner preference Receptor TypeAntagonist I: Mineralocorticoid Receptor (MR)Spironolactone II: Glucocorticoid Receptor (GR)RU-486

6. EXPERIMENT 1 Aragona and Wang 2008

7. EXPERIMENT 1: RESULTS

8. EXPERIMENT 2 Pair bonds enhanced after GR blockade  GR blockade is rewarding in females? Hypothesis ▫GR blockade interacts with central dopamine systems (D 1 and D 2 ) of the “reward circuitry” Approach ▫Pre-treat females with dopamine receptor antagonists before RU-486 treatment ▫Observe behavioral effects

9. EXPERIMENT 2: RESULTS ReceptorAntagonist D 1 and D 2 Haloperidol D1D1 SCH-23390 D2D2 Eticlopride

10. CONCLUSIONS Acute blockade of MRs and GRs facilitates pair bond formation in females Acute reduction of GR activation increases reward value of male Dopamine receptor antagonists can inhibit the effect of GR antagonists

11. DISCUSSION: GR BLOCKADE AND PAIR BONDING Activation of GR and MRs produce opposing actions on different measures of other species RU-486 and spironolactone have anti-gonadal effects ▫Enhanced pair bonding does not seem to result from these effects Spironolactone treatment affects other behaviors ▫Suggests it acts centrally ▫Greatest concentration of MR found in hippocampus, which may alter activity of ventral tegmental area (VTA)

12. DISCUSSION: GR INTERACTION WITH DOPAMINE D 1 and D 2 blockade antagonizes GR blockade by RU-486 Effects of D 1 receptor blockade were unexpected: ▫Previous studies indicate D 1 blockade does not interfere with mating-induced partner preference ▫Mating and pair bonding involve different mechanisms? Effects of D 2 receptor were expected: ▫Has been found to play major role in pair bonds ▫Social stress alters dopamine release in NAcc (also implicated in prairie vole pair bonding)  Corticosterone interact with dopamine in NAcc