Acute amphetamine exposure selectively desensitizes κ-opioid receptors in the nucleus accumbens

Yan Fang Xia, Li He, Jennifer Whistler, Gregory O. Hjelmstad

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

In the present study, we investigated the effects of psychostimulant exposure on κ-opioid peptide (KOP) receptor signaling in the rat mesolimbic system. A single subcutaneous (s.c.) injection of amphetamine (2.5 mg/kg) reduced the KOP receptor-mediated inhibition of glutamate release in the nucleus accumbens shell, as a consequence of KOP receptor desensitization. This effect was blocked by dopamine (DA) receptor antagonists or the nonselective opioid antagonist, naltrexone (1 mg/kg, s.c.), and mimicked by the KOP receptor agonists U69593 (0.32 mg/kg, s.c.) and dynorphin (1 μM), indicating that an amphetamine-induced release of dynorphin is producing a long-lasting desensitization of the KOP receptor. Despite the fact that amphetamine also increases dynorphin release in the ventral tegmental area (VTA), KOP receptor function in this region was not affected by amphetamine; there was no difference in the KOP receptor-mediated change in firing rate or resting membrane potential measured in VTA neurons from saline- or amphetamine-treated animals. This study demonstrates that amphetamine can produce regionally selective adaptations in KOP receptor signaling, which may, in turn, alter the effects of subsequent drug exposure.

Original languageEnglish (US)
Pages (from-to)892-900
Number of pages9
JournalNeuropsychopharmacology
Volume33
Issue number4
DOIs
StatePublished - Mar 1 2008
Externally publishedYes

Fingerprint

Nucleus Accumbens
Opioid Receptors
Amphetamine
Dynorphins
Ventral Tegmental Area
Naltrexone
Peptide Receptors
Opioid Peptides
Narcotic Antagonists
Dopamine Antagonists
Subcutaneous Injections
Membrane Potentials
Glutamic Acid
Neurons
Pharmaceutical Preparations

Keywords

  • κ-opioid
  • Addiction
  • Amphetamine
  • Desensitization
  • Nucleus accumbens
  • Ventral tegmental area

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health

Cite this

Acute amphetamine exposure selectively desensitizes κ-opioid receptors in the nucleus accumbens. / Xia, Yan Fang; He, Li; Whistler, Jennifer; Hjelmstad, Gregory O.

In: Neuropsychopharmacology, Vol. 33, No. 4, 01.03.2008, p. 892-900.

Research output: Contribution to journalArticle

@article{86066a74fa5743c6a9dbab5b6d1df4b9,
title = "Acute amphetamine exposure selectively desensitizes κ-opioid receptors in the nucleus accumbens",
abstract = "In the present study, we investigated the effects of psychostimulant exposure on κ-opioid peptide (KOP) receptor signaling in the rat mesolimbic system. A single subcutaneous (s.c.) injection of amphetamine (2.5 mg/kg) reduced the KOP receptor-mediated inhibition of glutamate release in the nucleus accumbens shell, as a consequence of KOP receptor desensitization. This effect was blocked by dopamine (DA) receptor antagonists or the nonselective opioid antagonist, naltrexone (1 mg/kg, s.c.), and mimicked by the KOP receptor agonists U69593 (0.32 mg/kg, s.c.) and dynorphin (1 μM), indicating that an amphetamine-induced release of dynorphin is producing a long-lasting desensitization of the KOP receptor. Despite the fact that amphetamine also increases dynorphin release in the ventral tegmental area (VTA), KOP receptor function in this region was not affected by amphetamine; there was no difference in the KOP receptor-mediated change in firing rate or resting membrane potential measured in VTA neurons from saline- or amphetamine-treated animals. This study demonstrates that amphetamine can produce regionally selective adaptations in KOP receptor signaling, which may, in turn, alter the effects of subsequent drug exposure.",
keywords = "κ-opioid, Addiction, Amphetamine, Desensitization, Nucleus accumbens, Ventral tegmental area",
author = "Xia, {Yan Fang} and Li He and Jennifer Whistler and Hjelmstad, {Gregory O.}",
year = "2008",
month = "3",
day = "1",
doi = "10.1038/sj.npp.1301463",
language = "English (US)",
volume = "33",
pages = "892--900",
journal = "Neuropsychopharmacology",
issn = "0893-133X",
publisher = "Nature Publishing Group",
number = "4",

}

TY - JOUR

T1 - Acute amphetamine exposure selectively desensitizes κ-opioid receptors in the nucleus accumbens

AU - Xia, Yan Fang

AU - He, Li

AU - Whistler, Jennifer

AU - Hjelmstad, Gregory O.

PY - 2008/3/1

Y1 - 2008/3/1

N2 - In the present study, we investigated the effects of psychostimulant exposure on κ-opioid peptide (KOP) receptor signaling in the rat mesolimbic system. A single subcutaneous (s.c.) injection of amphetamine (2.5 mg/kg) reduced the KOP receptor-mediated inhibition of glutamate release in the nucleus accumbens shell, as a consequence of KOP receptor desensitization. This effect was blocked by dopamine (DA) receptor antagonists or the nonselective opioid antagonist, naltrexone (1 mg/kg, s.c.), and mimicked by the KOP receptor agonists U69593 (0.32 mg/kg, s.c.) and dynorphin (1 μM), indicating that an amphetamine-induced release of dynorphin is producing a long-lasting desensitization of the KOP receptor. Despite the fact that amphetamine also increases dynorphin release in the ventral tegmental area (VTA), KOP receptor function in this region was not affected by amphetamine; there was no difference in the KOP receptor-mediated change in firing rate or resting membrane potential measured in VTA neurons from saline- or amphetamine-treated animals. This study demonstrates that amphetamine can produce regionally selective adaptations in KOP receptor signaling, which may, in turn, alter the effects of subsequent drug exposure.

AB - In the present study, we investigated the effects of psychostimulant exposure on κ-opioid peptide (KOP) receptor signaling in the rat mesolimbic system. A single subcutaneous (s.c.) injection of amphetamine (2.5 mg/kg) reduced the KOP receptor-mediated inhibition of glutamate release in the nucleus accumbens shell, as a consequence of KOP receptor desensitization. This effect was blocked by dopamine (DA) receptor antagonists or the nonselective opioid antagonist, naltrexone (1 mg/kg, s.c.), and mimicked by the KOP receptor agonists U69593 (0.32 mg/kg, s.c.) and dynorphin (1 μM), indicating that an amphetamine-induced release of dynorphin is producing a long-lasting desensitization of the KOP receptor. Despite the fact that amphetamine also increases dynorphin release in the ventral tegmental area (VTA), KOP receptor function in this region was not affected by amphetamine; there was no difference in the KOP receptor-mediated change in firing rate or resting membrane potential measured in VTA neurons from saline- or amphetamine-treated animals. This study demonstrates that amphetamine can produce regionally selective adaptations in KOP receptor signaling, which may, in turn, alter the effects of subsequent drug exposure.

KW - κ-opioid

KW - Addiction

KW - Amphetamine

KW - Desensitization

KW - Nucleus accumbens

KW - Ventral tegmental area

UR - http://www.scopus.com/inward/record.url?scp=39149110268&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=39149110268&partnerID=8YFLogxK

U2 - 10.1038/sj.npp.1301463

DO - 10.1038/sj.npp.1301463

M3 - Article

VL - 33

SP - 892

EP - 900

JO - Neuropsychopharmacology

JF - Neuropsychopharmacology

SN - 0893-133X

IS - 4

ER -