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PACAP Signalling Network in the Nucleus Accumbens Core Regulates Reinstatement Behaviour in Rat
Samrat Bose1, Gregory Simandl1, Evan M Hess1
1Department of Biomedical Sciences, Marquette University, Milwaukee, Wisconsin, USA.
Addiction Biology
|October 2, 2025
Summary
Pituitary adenylate cyclase-activating polypeptide (PACAP) signaling in the nucleus accumbens core shows potential for treating cocaine use disorder by blocking drug relapse. This neuropeptide may offer circuit-selective neuromodulation without widespread brain disruption.
Area of Science:
- Neuroscience
- Pharmacology
- Addiction Research
Background:
- Cocaine use disorder (CUD) lacks effective FDA-approved treatments.
- Developing circuit-selective therapeutics is challenging.
- Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide with potential for neuromodulation.
Purpose of the Study:
- Investigate the presence and function of endogenous PACAP signaling in the rat nucleus accumbens core (NAcc).
- Determine PACAP's effect on cocaine-seeking behavior and reinstatement.
Main Methods:
- Measured endogenous PACAP and PAC1 receptor expression in the NAcc.
- Administered PACAP infusions into the NAcc.
- Assessed effects on cocaine-primed reinstatement and dopamine agonist-induced reinstatement.
Main Results:
- PACAP and PAC1R are endogenously expressed in the rat NAcc.
- Intra-NAcc PACAP blocked cocaine-primed reinstatement.
- PACAP blocked reinstatement induced by a D1-like dopamine receptor agonist but not a D2-like agonist.
Conclusions:
- Endogenous PACAP signaling in the NAcc modulates cocaine seeking behavior.
- PACAP may offer a novel therapeutic target for CUD by selectively interfering with specific dopamine pathways.
- Further research is needed to elucidate PACAP's full therapeutic potential for addiction.
