Effects of subchronic methamphetamine exposure on basal dopamine and stress-induced dopamine release in the nucleus accumbens shell of rats

Susan L. Broom, Bryan Yamamoto

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

Rationale: Subchronic administration of stimulants reduces basal dopamine (DA) concentrations and blocks stress-induced DA release in the nucleus accumbens (NA) of rats during withdrawal. However, no studies have attempted to relate early withdrawal from chronic drug exposure to stress reactivity and changes in DA transmission. Objectives: The effects of subchronic low-dose methamphetamine (METH) administration on regional changes in dopamine transporter (DAT) and norepinephrine transporter (NET) immunoreactivity and function during early withdrawal were examined. The effects of subchronic METH on stress responsivity measured by DA release in the nucleus accumbens shell (NA SHELL) and core (NA CORE) during acute restraint stress were also examined. Methods: Male rats received single injections of METH (2.0 mg/kg i.p.) or saline (SAL) for 10 days and then were killed 24 h after the last injection. DAT and NET protein in NA, striatum (STR), medial prefrontal cortex (mPFC), and hippocampus were assayed by Western blot analysis. Experiment 2 measured basal extracellular DA concentrations and restraint-stress-induced DA release in vivo in the NA SHELL and CORE of SAL- and METH-pretreated rats after 24-h withdrawal. Experiment 3 examined the in vivo regulation of extracellular DA in the NA SHELL and/or CORE after local administration of GBR12909 (50 μM) or nisoxetine (100 μM; NA SHELL). Results: Subchronic METH increased DAT but not NET immunoreactivity in the NA compared to the STR and mPFC. METH reduced basal extracellular DA and blocked restraint-stress-induced DA release in the NA SHELL. DA uptake blockade increased extracellular DA more in the NA SHELL of METH rats, whereas NE uptake blockade increased basal DA concentrations to a similar extent in METH and SAL rats. Conclusions: These results suggest that subchronic METH exposure selectively increases NA DAT and consequently reduces basal and stress-induced DA release in the NA SHELL during early withdrawal.

Original languageEnglish (US)
Pages (from-to)467-476
Number of pages10
JournalPsychopharmacology
Volume181
Issue number3
DOIs
StatePublished - Sep 2005
Externally publishedYes

Fingerprint

Methamphetamine
Nucleus Accumbens
Dopamine
Dopamine Plasma Membrane Transport Proteins
Norepinephrine Plasma Membrane Transport Proteins
nisoxetine
Prefrontal Cortex
Injections
Hippocampus

Keywords

  • Dopamine transporter
  • GBR12909
  • In vivo microdialysis
  • Nisoxetine
  • Norepinephrine transporter
  • Nucleus accumbens
  • Psychostimulants
  • Stress
  • Western blot

ASJC Scopus subject areas

  • Pharmacology

Cite this

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title = "Effects of subchronic methamphetamine exposure on basal dopamine and stress-induced dopamine release in the nucleus accumbens shell of rats",
abstract = "Rationale: Subchronic administration of stimulants reduces basal dopamine (DA) concentrations and blocks stress-induced DA release in the nucleus accumbens (NA) of rats during withdrawal. However, no studies have attempted to relate early withdrawal from chronic drug exposure to stress reactivity and changes in DA transmission. Objectives: The effects of subchronic low-dose methamphetamine (METH) administration on regional changes in dopamine transporter (DAT) and norepinephrine transporter (NET) immunoreactivity and function during early withdrawal were examined. The effects of subchronic METH on stress responsivity measured by DA release in the nucleus accumbens shell (NA SHELL) and core (NA CORE) during acute restraint stress were also examined. Methods: Male rats received single injections of METH (2.0 mg/kg i.p.) or saline (SAL) for 10 days and then were killed 24 h after the last injection. DAT and NET protein in NA, striatum (STR), medial prefrontal cortex (mPFC), and hippocampus were assayed by Western blot analysis. Experiment 2 measured basal extracellular DA concentrations and restraint-stress-induced DA release in vivo in the NA SHELL and CORE of SAL- and METH-pretreated rats after 24-h withdrawal. Experiment 3 examined the in vivo regulation of extracellular DA in the NA SHELL and/or CORE after local administration of GBR12909 (50 μM) or nisoxetine (100 μM; NA SHELL). Results: Subchronic METH increased DAT but not NET immunoreactivity in the NA compared to the STR and mPFC. METH reduced basal extracellular DA and blocked restraint-stress-induced DA release in the NA SHELL. DA uptake blockade increased extracellular DA more in the NA SHELL of METH rats, whereas NE uptake blockade increased basal DA concentrations to a similar extent in METH and SAL rats. Conclusions: These results suggest that subchronic METH exposure selectively increases NA DAT and consequently reduces basal and stress-induced DA release in the NA SHELL during early withdrawal.",
keywords = "Dopamine transporter, GBR12909, In vivo microdialysis, Nisoxetine, Norepinephrine transporter, Nucleus accumbens, Psychostimulants, Stress, Western blot",
author = "Broom, {Susan L.} and Bryan Yamamoto",
year = "2005",
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doi = "10.1007/s00213-005-0007-6",
language = "English (US)",
volume = "181",
pages = "467--476",
journal = "Psychopharmacology",
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publisher = "Springer Verlag",
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TY - JOUR

T1 - Effects of subchronic methamphetamine exposure on basal dopamine and stress-induced dopamine release in the nucleus accumbens shell of rats

AU - Broom, Susan L.

AU - Yamamoto, Bryan

PY - 2005/9

Y1 - 2005/9

N2 - Rationale: Subchronic administration of stimulants reduces basal dopamine (DA) concentrations and blocks stress-induced DA release in the nucleus accumbens (NA) of rats during withdrawal. However, no studies have attempted to relate early withdrawal from chronic drug exposure to stress reactivity and changes in DA transmission. Objectives: The effects of subchronic low-dose methamphetamine (METH) administration on regional changes in dopamine transporter (DAT) and norepinephrine transporter (NET) immunoreactivity and function during early withdrawal were examined. The effects of subchronic METH on stress responsivity measured by DA release in the nucleus accumbens shell (NA SHELL) and core (NA CORE) during acute restraint stress were also examined. Methods: Male rats received single injections of METH (2.0 mg/kg i.p.) or saline (SAL) for 10 days and then were killed 24 h after the last injection. DAT and NET protein in NA, striatum (STR), medial prefrontal cortex (mPFC), and hippocampus were assayed by Western blot analysis. Experiment 2 measured basal extracellular DA concentrations and restraint-stress-induced DA release in vivo in the NA SHELL and CORE of SAL- and METH-pretreated rats after 24-h withdrawal. Experiment 3 examined the in vivo regulation of extracellular DA in the NA SHELL and/or CORE after local administration of GBR12909 (50 μM) or nisoxetine (100 μM; NA SHELL). Results: Subchronic METH increased DAT but not NET immunoreactivity in the NA compared to the STR and mPFC. METH reduced basal extracellular DA and blocked restraint-stress-induced DA release in the NA SHELL. DA uptake blockade increased extracellular DA more in the NA SHELL of METH rats, whereas NE uptake blockade increased basal DA concentrations to a similar extent in METH and SAL rats. Conclusions: These results suggest that subchronic METH exposure selectively increases NA DAT and consequently reduces basal and stress-induced DA release in the NA SHELL during early withdrawal.

AB - Rationale: Subchronic administration of stimulants reduces basal dopamine (DA) concentrations and blocks stress-induced DA release in the nucleus accumbens (NA) of rats during withdrawal. However, no studies have attempted to relate early withdrawal from chronic drug exposure to stress reactivity and changes in DA transmission. Objectives: The effects of subchronic low-dose methamphetamine (METH) administration on regional changes in dopamine transporter (DAT) and norepinephrine transporter (NET) immunoreactivity and function during early withdrawal were examined. The effects of subchronic METH on stress responsivity measured by DA release in the nucleus accumbens shell (NA SHELL) and core (NA CORE) during acute restraint stress were also examined. Methods: Male rats received single injections of METH (2.0 mg/kg i.p.) or saline (SAL) for 10 days and then were killed 24 h after the last injection. DAT and NET protein in NA, striatum (STR), medial prefrontal cortex (mPFC), and hippocampus were assayed by Western blot analysis. Experiment 2 measured basal extracellular DA concentrations and restraint-stress-induced DA release in vivo in the NA SHELL and CORE of SAL- and METH-pretreated rats after 24-h withdrawal. Experiment 3 examined the in vivo regulation of extracellular DA in the NA SHELL and/or CORE after local administration of GBR12909 (50 μM) or nisoxetine (100 μM; NA SHELL). Results: Subchronic METH increased DAT but not NET immunoreactivity in the NA compared to the STR and mPFC. METH reduced basal extracellular DA and blocked restraint-stress-induced DA release in the NA SHELL. DA uptake blockade increased extracellular DA more in the NA SHELL of METH rats, whereas NE uptake blockade increased basal DA concentrations to a similar extent in METH and SAL rats. Conclusions: These results suggest that subchronic METH exposure selectively increases NA DAT and consequently reduces basal and stress-induced DA release in the NA SHELL during early withdrawal.

KW - Dopamine transporter

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KW - In vivo microdialysis

KW - Nisoxetine

KW - Norepinephrine transporter

KW - Nucleus accumbens

KW - Psychostimulants

KW - Stress

KW - Western blot

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