Regional and sex differences in spontaneous striatal dopamine transmission

J Neurochem. 2022 Mar;160(6):598-612. doi: 10.1111/jnc.15473. Epub 2021 Aug 16.

Abstract

Striatal dopamine release is key for learning and motivation and is composed of subregions including the dorsal striatum (DS), nucleus accumbens core, and the nucleus accumbens shell. Spontaneously occurring dopamine release was compared across these subregions. Dopamine release/uptake dynamics differ across striatal subregions, with dopamine transient release amplitude and release frequency greatest in male mice, and the largest signals observed in the DS. Surprisingly, female mice exhibited little regional differences in dopamine release for DS and nucleus accumbens core regions, but lower release in the nucleus accumbens shell. Blocking voltage-gated K+ channel (Kv channels) with 4-aminopyridine enhanced dopamine detection without affecting reuptake. The 4-aminopyridine effects were greatest in ventral regions of female mice, suggesting regional differences in Kv channel expression. The dopamine transporter blocker cocaine also enhanced detection across subregions in both sexes, with greater overall increased release in females than males. Thus, sex differences in dopamine transmission are apparent and likely include differences in the Kv channel and dopamine transporter function. The lack of regional differences in dopamine release observed in females indicates differential regulation of spontaneous and evoked dopamine release.

Keywords: Kv channels; accumbens; cocaine; dopamine; sex differences; striatum.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 4-Aminopyridine / metabolism
  • Animals
  • Cocaine* / metabolism
  • Cocaine* / pharmacology
  • Corpus Striatum / metabolism
  • Dopamine Antagonists
  • Dopamine Plasma Membrane Transport Proteins / metabolism
  • Dopamine* / metabolism
  • Female
  • Male
  • Mice
  • Nucleus Accumbens / metabolism
  • Sex Characteristics

Substances

  • Dopamine Antagonists
  • Dopamine Plasma Membrane Transport Proteins
  • 4-Aminopyridine
  • Cocaine
  • Dopamine