Aversion-induced dopamine reductions predict drug-taking and escape behaviors. Neuropsychopharmacology 2025 Aug;50(9):1376-1384
Date
04/10/2025Pubmed ID
40205012Pubmed Central ID
PMC12259906DOI
10.1038/s41386-025-02101-7Scopus ID
2-s2.0-105002178285 (requires institutional sign-in at Scopus site) 1 CitationAbstract
Dopamine release in the nucleus accumbens core (NAcC) has long been associated with the promotion of motivated behavior. However, inhibited dopamine signaling can increase behavior in certain settings, such as during drug self-administration. While aversive environmental stimuli can reduce dopamine, it is unclear whether such stimuli reliably engage this mechanism in different contexts. Here we compared the physiological and behavioral responses to the same aversive stimulus in different designs to determine if there is uniformity in the manner that aversive stimuli are encoded and promote behavior. NAcC dopamine was measured using fiber photometry in male and female rats during cocaine self-administration sessions in which an acutely aversive 90 dB white noise was intermittently presented. In a separate group of rats, aversion-induced changes in dopamine were measured during an escape design in which operant responses terminated aversive white noise. Aversive white noise significantly reduced NAcC dopamine and increased cocaine self-administration in both male and female rats. The same relationship was observed in the escape design, in which white noise reduced dopamine and promoted the performance of escape behavior. In both designs, the magnitude of the dopamine reduction predicted behavioral performance. While prior research demonstrated that pharmacologically reduced dopamine signaling can promote intake, this report demonstrates that this physiological mechanism is naturally engaged by aversive environmental stimuli and is generalizable to non-drug contexts. These findings illustrate a common physiological signature in response to aversion that may promote both adaptive and maladaptive behavior.
Author List
Grafelman EM, Côté BE, Vlach L, Geise E, Padula GN, Wheeler DS, Hearing MC, Mantsch JR, Wheeler RAAuthor
John Mantsch PhD Chair, Professor in the Pharmacology and Toxicology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Acoustic StimulationAnimals
Avoidance Learning
Cocaine
Conditioning, Operant
Dopamine
Dopamine Uptake Inhibitors
Escape Reaction
Female
Male
Nucleus Accumbens
Rats
Rats, Sprague-Dawley
Self Administration
