Systemic Oxytocin Administration Alters Mesolimbic Dopamine Release in Mice

Neuroscience. 2019 Jun 1;408:226-238. doi: 10.1016/j.neuroscience.2019.04.006. Epub 2019 Apr 11.

Abstract

Growing research indicates oxytocin may be involved in relieving anxiety and attenuating the rewarding effects of psychostimulants. This study investigated the effects of subchronic oxytocin treatments on mesolimbic dopamine transmission in areas associated with anxiety and addiction, the amygdala and the nucleus accumbens (NAc), respectively. Using in vivo fixed potential amperometry, stimulation-evoked dopamine release was recorded in anesthetized mice pretreated with subchronic oxytocin (four i.p. injections of 1 mg/kg oxytocin or saline with 48 h between injections). During dopamine recordings, mice received an i.p. drug challenge of either oxytocin (1 mg/kg), the dopamine reuptake blocker nomifensine (10 mg/kg), or saline. Overall, subchronic oxytocin pretreatment did alter properties of dopamine release in these limbic structures. In the amygdala, dopamine release was decreased following the oxytocin challenge but only in oxytocin pretreated mice. In the NAc, baseline dopamine release was attenuated in oxytocin pretreated mice relative to saline pretreated mice. Furthermore, oxytocin pretreated mice displayed a reduced dopaminergic response to the drug challenge of nomifensine relative to control mice. Together these results suggest that oxytocin may be useful at treating aspects of anxiety and drug abuse. Elucidating the neural effects of oxytocin is critical given the multitude of potential therapeutic uses for this drug.

Keywords: addiction; amperometry; amygdala; anxiety; cocaine; nucleus accumbens.

MeSH terms

  • Amygdala / drug effects*
  • Amygdala / metabolism
  • Animals
  • Dopamine / metabolism*
  • Dopamine Uptake Inhibitors / pharmacology
  • Male
  • Mice
  • Neurons / drug effects
  • Neurons / metabolism
  • Nomifensine / pharmacology
  • Nucleus Accumbens / drug effects*
  • Nucleus Accumbens / metabolism
  • Oxytocin / pharmacology*

Substances

  • Dopamine Uptake Inhibitors
  • Nomifensine
  • Oxytocin
  • Dopamine