Methamphetamine Exposure During Development Causes Lasting Changes to Mesolimbic Dopamine Signaling in Mice

Cell Mol Neurobiol. 2022 Oct;42(7):2433-2438. doi: 10.1007/s10571-021-01120-4. Epub 2021 Jun 17.

Abstract

Methamphetamine (MA) abuse remains a public health issue. Prenatal MA exposure (PME) poses a significant health problem, as we know very little about the drug's long-term physiological impact on the developing human brain. We investigated the long-term consequences of early MA exposure using a mouse model that targets the brain growth spurt, which occurs during human third-trimester. Adult mice previously subjected to acute MA during post-natal days 4-9 exhibited hyperactivity during the Open-Field Test, while exhibiting no motor coordination changes during the Rotarod Test. Neonatal MA exposure reduced basal dopamine (DA) uptake rates in adult nucleus accumbens slices compared with saline-injected controls. Although slices from neonatal MA-exposed mice showed no change in evoked DA signals in the presence of MA, they exhibited potentiated non-evoked DA release through DA efflux in response to MA. These data suggest that developmental MA exposure alters brain development to produce long-lasting physiological changes to the adult mesolimbic DA system, as well as altering responses to acute MA exposure in adulthood. This study provides new insights into an important, under-investigated area in drugs of abuse research.

Keywords: Development; Dopamine; Fast-scan cyclic voltammetry; Methamphetamine; Prenatal methamphetamine exposure.

MeSH terms

  • Adult
  • Animals
  • Brain
  • Dopamine
  • Female
  • Humans
  • Methamphetamine*
  • Nucleus Accumbens
  • Pregnancy
  • Rotarod Performance Test

Substances

  • Methamphetamine
  • Dopamine