Kappa Opioid Receptors Negatively Regulate Real Time Spontaneous Dopamine Signals by Reducing Release and Increasing...

Area of Science:

• Neuroscience
• Pharmacology
• Neurochemistry

Background:

• The dynorphin/kappa opioid receptor (KOR) system modulates dopamine (DA) neurotransmission.
• KOR activation is known to decrease extracellular DA and enhance DA transporter (DAT) function.

Approach:

• Utilized fiber photometry with the dLight1.2 photosensor in freely moving male and female mice.
• Measured real-time DA fluctuations in the nucleus accumbens (NAc) core.
• Administered the KOR agonist U50,488H (U50) with or without the KOR antagonist aticaprant (ATIC).

Key Points:

• KOR activation reduced the amplitude and width of spontaneous DA signals in males, and reduced width in females.
• Increased correlation slope between amplitude and width indicated enhanced DA uptake rates in both sexes.
• KOR activation decreased the frequency of DA signals, with stronger effects observed in males.
• KORs inhibit DA release, promote DAT-mediated uptake, and reduce signal frequency.

Conclusions:

• KORs exert significant inhibitory control over spontaneous DA signaling in the NAc core.
• KOR activation influences DA signaling through inhibition of DA release, promotion of DAT-mediated uptake, and reduction in signal frequency.
• Sex-dependent differences exist in the magnitude of KOR system's inhibitory effects on DA signaling.