Profound reduction in sensitivity to the aversive effects of methamphetamine in mice bred for high methamphetamine intake

Shkelzen Shabani, Carrie S. McKinnon, Christopher Cunningham, Tamara Phillips

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Reduced sensitivity to aversive effects of methamphetamine (MA) may increase risk for MA abuse. Studies in two replicate sets of mouse lines that were selectively bred for high and low levels of MA intake support this view. Current studies examined the extent of insensitivity to aversive MA effects of mice bred for high levels of MA drinking. Conditioning procedures in which drugs are delivered shortly after cue exposure have been used to detect aversive drug effects and, in some cases, are more sensitive to such effects. Aversive effects induced by MA injected immediately after exposure to cues from two different sensory modalities were examined. In addition, effects of higher MA doses than those used previously were examined. MA-associated place conditioning utilized tactile cues, whereas MA-induced taste conditioning utilized a novel tastant. Second replicate, MA high drinking (MAHDR-2) and low drinking (MALDR-2) mice were treated with doses of MA up to 4 mg/kg. MAHDR-2 mice were insensitive to aversive effects of MA, except after place conditioning with the 4 mg/kg dose; MALDR-2 mice exhibited sensitivity to aversive effects of MA at doses as low as 1 mg/kg. These studies show that the expression of aversion is dependent upon procedure and MA dose, and that MAHDR-2 mice have markedly reduced sensitivity to the aversive effects of MA. The current and previous results support a strong genetic relationship between level of MA intake and level of sensitivity to aversive effects of MA, a factor that could impact risk for MA use in humans.

Original languageEnglish (US)
Pages (from-to)1134-1141
Number of pages8
JournalNeuropharmacology
Volume62
Issue number2
DOIs
StatePublished - Feb 2012

Fingerprint

Methamphetamine
Drinking
Cues
Touch

Keywords

  • Addiction
  • Conditioned place aversion
  • Conditioned taste aversion
  • Drug reward
  • Selective breeding

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

Cite this

Profound reduction in sensitivity to the aversive effects of methamphetamine in mice bred for high methamphetamine intake. / Shabani, Shkelzen; McKinnon, Carrie S.; Cunningham, Christopher; Phillips, Tamara.

In: Neuropharmacology, Vol. 62, No. 2, 02.2012, p. 1134-1141.

Research output: Contribution to journalArticle

@article{a8fe019bf36140208244680f7eff8a6d,
title = "Profound reduction in sensitivity to the aversive effects of methamphetamine in mice bred for high methamphetamine intake",
abstract = "Reduced sensitivity to aversive effects of methamphetamine (MA) may increase risk for MA abuse. Studies in two replicate sets of mouse lines that were selectively bred for high and low levels of MA intake support this view. Current studies examined the extent of insensitivity to aversive MA effects of mice bred for high levels of MA drinking. Conditioning procedures in which drugs are delivered shortly after cue exposure have been used to detect aversive drug effects and, in some cases, are more sensitive to such effects. Aversive effects induced by MA injected immediately after exposure to cues from two different sensory modalities were examined. In addition, effects of higher MA doses than those used previously were examined. MA-associated place conditioning utilized tactile cues, whereas MA-induced taste conditioning utilized a novel tastant. Second replicate, MA high drinking (MAHDR-2) and low drinking (MALDR-2) mice were treated with doses of MA up to 4 mg/kg. MAHDR-2 mice were insensitive to aversive effects of MA, except after place conditioning with the 4 mg/kg dose; MALDR-2 mice exhibited sensitivity to aversive effects of MA at doses as low as 1 mg/kg. These studies show that the expression of aversion is dependent upon procedure and MA dose, and that MAHDR-2 mice have markedly reduced sensitivity to the aversive effects of MA. The current and previous results support a strong genetic relationship between level of MA intake and level of sensitivity to aversive effects of MA, a factor that could impact risk for MA use in humans.",
keywords = "Addiction, Conditioned place aversion, Conditioned taste aversion, Drug reward, Selective breeding",
author = "Shkelzen Shabani and McKinnon, {Carrie S.} and Christopher Cunningham and Tamara Phillips",
year = "2012",
month = "2",
doi = "10.1016/j.neuropharm.2011.11.005",
language = "English (US)",
volume = "62",
pages = "1134--1141",
journal = "Neuropharmacology",
issn = "0028-3908",
publisher = "Elsevier Limited",
number = "2",

}

TY - JOUR

T1 - Profound reduction in sensitivity to the aversive effects of methamphetamine in mice bred for high methamphetamine intake

AU - Shabani, Shkelzen

AU - McKinnon, Carrie S.

AU - Cunningham, Christopher

AU - Phillips, Tamara

PY - 2012/2

Y1 - 2012/2

N2 - Reduced sensitivity to aversive effects of methamphetamine (MA) may increase risk for MA abuse. Studies in two replicate sets of mouse lines that were selectively bred for high and low levels of MA intake support this view. Current studies examined the extent of insensitivity to aversive MA effects of mice bred for high levels of MA drinking. Conditioning procedures in which drugs are delivered shortly after cue exposure have been used to detect aversive drug effects and, in some cases, are more sensitive to such effects. Aversive effects induced by MA injected immediately after exposure to cues from two different sensory modalities were examined. In addition, effects of higher MA doses than those used previously were examined. MA-associated place conditioning utilized tactile cues, whereas MA-induced taste conditioning utilized a novel tastant. Second replicate, MA high drinking (MAHDR-2) and low drinking (MALDR-2) mice were treated with doses of MA up to 4 mg/kg. MAHDR-2 mice were insensitive to aversive effects of MA, except after place conditioning with the 4 mg/kg dose; MALDR-2 mice exhibited sensitivity to aversive effects of MA at doses as low as 1 mg/kg. These studies show that the expression of aversion is dependent upon procedure and MA dose, and that MAHDR-2 mice have markedly reduced sensitivity to the aversive effects of MA. The current and previous results support a strong genetic relationship between level of MA intake and level of sensitivity to aversive effects of MA, a factor that could impact risk for MA use in humans.

AB - Reduced sensitivity to aversive effects of methamphetamine (MA) may increase risk for MA abuse. Studies in two replicate sets of mouse lines that were selectively bred for high and low levels of MA intake support this view. Current studies examined the extent of insensitivity to aversive MA effects of mice bred for high levels of MA drinking. Conditioning procedures in which drugs are delivered shortly after cue exposure have been used to detect aversive drug effects and, in some cases, are more sensitive to such effects. Aversive effects induced by MA injected immediately after exposure to cues from two different sensory modalities were examined. In addition, effects of higher MA doses than those used previously were examined. MA-associated place conditioning utilized tactile cues, whereas MA-induced taste conditioning utilized a novel tastant. Second replicate, MA high drinking (MAHDR-2) and low drinking (MALDR-2) mice were treated with doses of MA up to 4 mg/kg. MAHDR-2 mice were insensitive to aversive effects of MA, except after place conditioning with the 4 mg/kg dose; MALDR-2 mice exhibited sensitivity to aversive effects of MA at doses as low as 1 mg/kg. These studies show that the expression of aversion is dependent upon procedure and MA dose, and that MAHDR-2 mice have markedly reduced sensitivity to the aversive effects of MA. The current and previous results support a strong genetic relationship between level of MA intake and level of sensitivity to aversive effects of MA, a factor that could impact risk for MA use in humans.

KW - Addiction

KW - Conditioned place aversion

KW - Conditioned taste aversion

KW - Drug reward

KW - Selective breeding

UR - http://www.scopus.com/inward/record.url?scp=84855940993&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84855940993&partnerID=8YFLogxK

U2 - 10.1016/j.neuropharm.2011.11.005

DO - 10.1016/j.neuropharm.2011.11.005

M3 - Article

C2 - 22118879

AN - SCOPUS:84855940993

VL - 62

SP - 1134

EP - 1141

JO - Neuropharmacology

JF - Neuropharmacology

SN - 0028-3908

IS - 2

ER -