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The Effects of AMPA Receptor Blockade in the Prelimbic Cortex on Systemic and Ventral Tegmental Area Opiate Reward Sensitivity

The Effects of AMPA Receptor Blockade in the Prelimbic Cortex on Systemic and Ventral Tegmental Area Opiate Reward Sensitivity

Xavier De Jaeger, Stephanie F Bishop, Tasha Ahmad, Danika Lyons, Garye Ami Ng, Steven R Laviolette

Psychopharmacology (Berl). 2013 Feb;225(3):687-95.

PMID: 22972411

Abstract:

Rationale:
The medial prefrontal cortex (mPFC) is a key neural region involved in opiate-related reward memory processing. AMPA receptor transmission in the mPFC modulates opiate-related reward memory processing, and chronic opiate exposure is associated with alterations in intra-mPFC AMPA receptor function.
Objective:
The objectives of this study were to examine how pharmacological blockade of AMPA receptor transmission in the prelimbic (PLC) division of the mPFC may modulate opiate reward memory acquisition and whether opiate exposure state may modulate the functional role of intra-PLC AMPA receptor transmission during opiate reward learning.
Methods:
Using an unbiased conditioned place preference (CPP) procedure in rats, we performed discrete, bilateral intra-PLC microinfusions of the AMPA receptor antagonist, 6,7-dinitroquinoxaline-2,3-dione, prior to behavioral morphine CPP conditioning, using sub-reward threshold conditioning doses of either systemic (0.05 mg/kg; i.p.) or intra-ventral tegmental area (VTA) morphine (250 ng/0.5 μl).
Results:
We show that, in both opiate-naïve and opiate-dependent states, intra-PLC blockade of AMPA receptor transmission, but not the infralimbic cortex, increases the behavioral reward magnitude of systemic or intra-VTA morphine. This effect is dependent on dopamine (DA)ergic signaling because pre-administration of cis-(Z)-flupenthixol-dihydrochloride (α-flu), a broad-spectrum dopamine receptor antagonist, blocked the morphine-reward potentiating effects of AMPA receptor blockade.
Conclusions:
These findings suggest a critical role for intra-PLC AMPA receptor transmission in the processing of opiate reward signaling. Furthermore, blockade of AMPA transmission specifically within the PLC is capable of switching opiate reward processing to a DA-dependent reward system, independently of previous opiate exposure history.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP51529012	cis-(Z)-Flupenthixol dihydrochloride		51529-01-2	Price

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