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Stress-induced neural activation is altered during early withdrawal from chronic methamphetamine

Jason S Jacobskind1, Zachary J Rosinger1, Morgan L Brooks1

  • 1University at Albany, Department of Psychology, Albany, NY 12222, United States.

Behavioural Brain Research
|March 24, 2019
PubMed

Insights

Chronic methamphetamine (MA) use causes depressive-like behaviors and alters brain responses to stress. This study found MA exposure reduced stress-induced neural activation in key brain regions, potentially explaining mood changes.

Area of Science:

  • Neuroscience
  • Psychiatry
  • Pharmacology

Background:

  • Chronic methamphetamine (MA) use is linked to depression and anxiety during abstinence.
  • MA may alter specific brain regions and activate microglia, potentially worsening stress-related behaviors.
  • Understanding MA's neurobiological effects is crucial for developing effective treatments.

Purpose of the Study:

  • To investigate how chronic MA exposure affects stress-induced neural activation in specific brain regions.
  • To examine the association between MA-induced neurobiological changes and behavioral alterations during withdrawal.
  • To determine if MA exposure alters microglial activation in the brain.

Main Methods:

  • Male and female mice received daily MA or saline injections for 10 days.
  • Behavioral tests (forced swim, nest building) were conducted during early withdrawal.
  • Immediate early gene (c-Fos) expression was measured to assess neural activation in response to forced swim stress.
  • Microglial numbers and activation states were examined in key brain regions.

Main Results:

  • Chronic MA exposure increased depressive-like behaviors (increased floating, decreased swimming) in both sexes.
  • MA-treated females exhibited impaired nest building, indicating distress-like behavior.
  • MA exposure attenuated c-Fos responses to stress in the central amygdala, hippocampus (CA3), prefrontal cortex, and bed nucleus of the stria terminalis (BST).
  • This attenuation in the BST was specific to males.
  • No changes in microglial numbers or activation were observed.

Conclusions:

  • Chronic MA use leads to depressive-like behaviors and sex-specific distress behaviors.
  • MA exposure attenuates neural activation in stress-related brain circuits during withdrawal.
  • This neurobiological dysregulation may underlie mood disturbances associated with chronic MA use.
  • Microglial activation does not appear to be a primary mechanism driving these effects.
Keywords:
Acute withdrawalForced swim testMethamphetamineMicrogliaStressc-Fos

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