Fall Research Expo 2020

Novel, Cell Type-Specific Roles for Nucleus Accumbens Amylin Receptors in Oxycodone Taking in Rats

The rise in prescription opioid use and availability in recent decades has led to widespread abuse and an overdose epidemic that still persists in the United States. Therefore, there is a critical need for research to investigate the neurobiological mechanisms of opioid use disorder and to identify molecular targets for pharmacotherapies that can reduce opioid abuse liability. Recent evidence suggests that one potential pharmaceutical target is the amylin system. Amylin is a glucoregulatory hormone that reduces oxycodone taking- and seeking-behaviors in rats when administered into the nucleus accumbens (NAc) shell, a brain region critical to opioid reinforcement. However, the cell type-specific mechanisms underlying amylin’s suppressive effects are unknown. The main cell populations in the NAc comprise dopamine D1 receptor-expressing medium spiny neurons (D1R-MSNs) and dopamine D2 receptor-expressing medium spiny neurons (D2R-MSNs). Evidence suggests that D1R-MSNs encode the reinforcing effects of opioids while D2R-MSNs encode aversive states such as withdrawal. This study sought to determine the functional significance of amylin receptors expressed on these two cell populations in oxycodone taking. Amylin receptor expression was selectively reduced in D1R- and D2R-MSNs using a knock-down virus. The results showed that reduced amylin receptor expression in D1R-MSNs, but not D2R-MSNs, facilitated the acquisition of oxycodone taking. These findings suggest that these two cell populations have different roles in the development of compulsive oxycodone-taking behavior. Furthermore, reduced amylin receptor expression in D1R- and D2R-MSNs attenuated amylin’s suppressive effects on oxycodone taking; thus, exogenous amylin reduces oxycodone taking via both cell types. Ultimately, the results from this study demonstrate that amylin receptors may serve as molecular targets to mitigate the compulsive behaviors that characterize opioid use disorder.

PRESENTED BY
PURM - Penn Undergraduate Research Mentoring Program
College of Arts & Sciences 2023
Join Jennifer for a virtual discussion
PRESENTED BY
PURM - Penn Undergraduate Research Mentoring Program
College of Arts & Sciences 2023

Comments

What a great presentation, Jennifer!  Is the normal developmental role(s) for D2R-MSNs known?  Since decreased expression of this receptor leads to decreased oxycodone taking (and presumably could serve as a surrogate for decreases in other addictive tendencies) is there evidence as to what might happen (ie side effects) if we did develop ways to target this receptor more broadly to reduce addiction onset/severity/etc.? 

Good job, Jennifer! Love the animations on the figures. Do you have any hypothesis on how amylin receptor activation regulates D1R- and D2R-MSNs to reduce opioid-taking behavior?

Well done, Jennifer! How will the effects of a CTR-A knockdown in D1R and D2R-MSNs be tested?

A very informative presentation and very comprehensive figures. Great job Jenn! Any theories about why D2R-MSNs may have no significant effect on drug acquisition but decrease oxycodone taking in rats?

Really informative poster! From these results, do you think that receptors such as the amylin receptor is what triggers the functional differences between D1R and D2R-MSNs?