Genetic analysis of sensitization and tolerance to cocaine

B. K. Tolliver, John Belknap, W. E. Woods, J. M. Carney

Research output: Contribution to journalArticle

61 Citations (Scopus)

Abstract

The present study investigated the effects of acute and repeated administration of cocaine (1.0-56.0 mg/kg) on locomotor activity in the genetically distinct DBA/2J and C57BL/6J inbred strains of mice. In addition, quantitative trait loci analysis of the effects of acute and repeated cocaine in 16 BXD recombinant inbred strains was used to provisionally detect and map minor gene loci which associate with cocaine responsiveness. Whereas locomotor activity was elevated maximally in both strains by 32 mg/kg of cocaine, DBA/2J mice were stimulated to a much greater extent than C57BL/6J mice. The stimulant effects of cocaine were diminished to control levels in DBA/2J mice after repeated daily injections, whereas cocaine-induced locomotion remained consistent in C57BL/6J mice throughout the 7-day testing period. Emergence of stereotyped behavior with repeated daily injections of 32 mg/kg of cocaine was observed in DBA/2J but not C57BL/6J mice. No differences in brain cocaine levels were found between the DBA/2J and C57BL/6J strains after acute or repeated injections. Quantitative trait loci analysis indicated significant associations of differences in cocaine responsiveness with marker loci on several chromosomes in the BXD recombinant inbred series. Those marker loci associated with the acute cocaine response were in most cases different from those markers associated with long-term responses. The current results demonstrate that genotype-dependent variation exists in behavioral responsiveness to cocaine in mice and suggest that the acute and long-term responses to cocaine may be under the control of separate sets of genes.

Original languageEnglish (US)
Pages (from-to)1230-1238
Number of pages9
JournalJournal of Pharmacology and Experimental Therapeutics
Volume270
Issue number3
StatePublished - 1994
Externally publishedYes

Fingerprint

Cocaine
Locomotion
Inbred C57BL Mouse
Inbred DBA Mouse
Quantitative Trait Loci
Injections
Stereotyped Behavior
Inbred Strains Mice
Genes
Chromosomes
Genotype

ASJC Scopus subject areas

  • Pharmacology

Cite this

Tolliver, B. K., Belknap, J., Woods, W. E., & Carney, J. M. (1994). Genetic analysis of sensitization and tolerance to cocaine. Journal of Pharmacology and Experimental Therapeutics, 270(3), 1230-1238.

Genetic analysis of sensitization and tolerance to cocaine. / Tolliver, B. K.; Belknap, John; Woods, W. E.; Carney, J. M.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 270, No. 3, 1994, p. 1230-1238.

Research output: Contribution to journalArticle

Tolliver, BK, Belknap, J, Woods, WE & Carney, JM 1994, 'Genetic analysis of sensitization and tolerance to cocaine', Journal of Pharmacology and Experimental Therapeutics, vol. 270, no. 3, pp. 1230-1238.
Tolliver, B. K. ; Belknap, John ; Woods, W. E. ; Carney, J. M. / Genetic analysis of sensitization and tolerance to cocaine. In: Journal of Pharmacology and Experimental Therapeutics. 1994 ; Vol. 270, No. 3. pp. 1230-1238.
@article{24fe57ac55d8450db98ed63871c4e02a,
title = "Genetic analysis of sensitization and tolerance to cocaine",
abstract = "The present study investigated the effects of acute and repeated administration of cocaine (1.0-56.0 mg/kg) on locomotor activity in the genetically distinct DBA/2J and C57BL/6J inbred strains of mice. In addition, quantitative trait loci analysis of the effects of acute and repeated cocaine in 16 BXD recombinant inbred strains was used to provisionally detect and map minor gene loci which associate with cocaine responsiveness. Whereas locomotor activity was elevated maximally in both strains by 32 mg/kg of cocaine, DBA/2J mice were stimulated to a much greater extent than C57BL/6J mice. The stimulant effects of cocaine were diminished to control levels in DBA/2J mice after repeated daily injections, whereas cocaine-induced locomotion remained consistent in C57BL/6J mice throughout the 7-day testing period. Emergence of stereotyped behavior with repeated daily injections of 32 mg/kg of cocaine was observed in DBA/2J but not C57BL/6J mice. No differences in brain cocaine levels were found between the DBA/2J and C57BL/6J strains after acute or repeated injections. Quantitative trait loci analysis indicated significant associations of differences in cocaine responsiveness with marker loci on several chromosomes in the BXD recombinant inbred series. Those marker loci associated with the acute cocaine response were in most cases different from those markers associated with long-term responses. The current results demonstrate that genotype-dependent variation exists in behavioral responsiveness to cocaine in mice and suggest that the acute and long-term responses to cocaine may be under the control of separate sets of genes.",
author = "Tolliver, {B. K.} and John Belknap and Woods, {W. E.} and Carney, {J. M.}",
year = "1994",
language = "English (US)",
volume = "270",
pages = "1230--1238",
journal = "Journal of Pharmacology and Experimental Therapeutics",
issn = "0022-3565",
publisher = "American Society for Pharmacology and Experimental Therapeutics",
number = "3",

}

TY - JOUR

T1 - Genetic analysis of sensitization and tolerance to cocaine

AU - Tolliver, B. K.

AU - Belknap, John

AU - Woods, W. E.

AU - Carney, J. M.

PY - 1994

Y1 - 1994

N2 - The present study investigated the effects of acute and repeated administration of cocaine (1.0-56.0 mg/kg) on locomotor activity in the genetically distinct DBA/2J and C57BL/6J inbred strains of mice. In addition, quantitative trait loci analysis of the effects of acute and repeated cocaine in 16 BXD recombinant inbred strains was used to provisionally detect and map minor gene loci which associate with cocaine responsiveness. Whereas locomotor activity was elevated maximally in both strains by 32 mg/kg of cocaine, DBA/2J mice were stimulated to a much greater extent than C57BL/6J mice. The stimulant effects of cocaine were diminished to control levels in DBA/2J mice after repeated daily injections, whereas cocaine-induced locomotion remained consistent in C57BL/6J mice throughout the 7-day testing period. Emergence of stereotyped behavior with repeated daily injections of 32 mg/kg of cocaine was observed in DBA/2J but not C57BL/6J mice. No differences in brain cocaine levels were found between the DBA/2J and C57BL/6J strains after acute or repeated injections. Quantitative trait loci analysis indicated significant associations of differences in cocaine responsiveness with marker loci on several chromosomes in the BXD recombinant inbred series. Those marker loci associated with the acute cocaine response were in most cases different from those markers associated with long-term responses. The current results demonstrate that genotype-dependent variation exists in behavioral responsiveness to cocaine in mice and suggest that the acute and long-term responses to cocaine may be under the control of separate sets of genes.

AB - The present study investigated the effects of acute and repeated administration of cocaine (1.0-56.0 mg/kg) on locomotor activity in the genetically distinct DBA/2J and C57BL/6J inbred strains of mice. In addition, quantitative trait loci analysis of the effects of acute and repeated cocaine in 16 BXD recombinant inbred strains was used to provisionally detect and map minor gene loci which associate with cocaine responsiveness. Whereas locomotor activity was elevated maximally in both strains by 32 mg/kg of cocaine, DBA/2J mice were stimulated to a much greater extent than C57BL/6J mice. The stimulant effects of cocaine were diminished to control levels in DBA/2J mice after repeated daily injections, whereas cocaine-induced locomotion remained consistent in C57BL/6J mice throughout the 7-day testing period. Emergence of stereotyped behavior with repeated daily injections of 32 mg/kg of cocaine was observed in DBA/2J but not C57BL/6J mice. No differences in brain cocaine levels were found between the DBA/2J and C57BL/6J strains after acute or repeated injections. Quantitative trait loci analysis indicated significant associations of differences in cocaine responsiveness with marker loci on several chromosomes in the BXD recombinant inbred series. Those marker loci associated with the acute cocaine response were in most cases different from those markers associated with long-term responses. The current results demonstrate that genotype-dependent variation exists in behavioral responsiveness to cocaine in mice and suggest that the acute and long-term responses to cocaine may be under the control of separate sets of genes.

UR - http://www.scopus.com/inward/record.url?scp=0027986486&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0027986486&partnerID=8YFLogxK

M3 - Article

VL - 270

SP - 1230

EP - 1238

JO - Journal of Pharmacology and Experimental Therapeutics

JF - Journal of Pharmacology and Experimental Therapeutics

SN - 0022-3565

IS - 3

ER -