Quantitative-trait loci analysis of cocaine-related behaviours and neurochemistry

Byron Jones, Lisa M. Tarantino, Lawrence A. Rodriguez, Cheryl L. Reed, Gerald E. McClearn, Robert Plomin, V. Gene Erwin

Research output: Contribution to journalArticle

65 Citations (Scopus)

Abstract

We recently conducted a dose-response study of the effects of cocaine on several activity measures in the panel of BxD/Ty recombinant inbred mice. Animals were tested in an automated activity chamber over 2 days with i.p. saline on day 1 and i.p. cocaine on day 2, at one of four doses, 5, 15, 30 or 45 mg kg-1. The monitor recorded total distance traveled, nosepokes in a holeboard, repeated movements and time spent by an individual in proximity to the centre of the apparatus. Dose-response curves for locomotor activation, i.e. the difference between cocaine and saline scores, showed that for all strains tested, scores increased 5-30 mg kg-1. With few exceptions, locomotor activity at 45 mg kg-1 was not significantly higher than that at 30 mg kg-1. Repeated movement scores showed patterns similar to locomotor activity and nosepokes tended to be progressively inhibited by increasing doses of cocaine. Recombinant inbred strain mean distributions for all behaviours and at all doses exhibited continuous, rather than discrete variation, thus providing evidence of multiple-gene effects on cocaine-related behaviours. Quantitative trait loci (QTL) analysis pointed to several chromosomal locations associated with variations in cocaine-related behaviours and some are either identical or close to QTL reported by others. In separate groups of animals, densities of dopamine D1, and D2 receptors and dopamine uptake transporters were measured in the medial prefrontal cortex, caudate-putamen, nucleus accumbens and ventral midbrain. In all areas, all measures showed distributions consistent with polygenic influence and were associated with QTL. Of particular interest was our finding of a large segment on chromosome 15, which is related to dopamine receptor densities and cocaine-related behaviours.

Original languageEnglish (US)
Pages (from-to)607-617
Number of pages11
JournalPharmacogenetics
Volume9
Issue number5
StatePublished - 1999
Externally publishedYes

Fingerprint

Neurochemistry
Quantitative Trait Loci
Cocaine
Locomotion
Chromosomes, Human, Pair 15
Dopamine D1 Receptors
Dopamine Plasma Membrane Transport Proteins
Dopamine D2 Receptors
Caudate Nucleus
Putamen
Dopamine Receptors
Nucleus Accumbens
Mesencephalon
Prefrontal Cortex

All Science Journal Classification (ASJC) codes

  • Genetics
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Jones, B., Tarantino, L. M., Rodriguez, L. A., Reed, C. L., McClearn, G. E., Plomin, R., & Erwin, V. G. (1999). Quantitative-trait loci analysis of cocaine-related behaviours and neurochemistry. Pharmacogenetics, 9(5), 607-617.

Quantitative-trait loci analysis of cocaine-related behaviours and neurochemistry. / Jones, Byron; Tarantino, Lisa M.; Rodriguez, Lawrence A.; Reed, Cheryl L.; McClearn, Gerald E.; Plomin, Robert; Erwin, V. Gene.

In: Pharmacogenetics, Vol. 9, No. 5, 1999, p. 607-617.

Research output: Contribution to journalArticle

Jones, B, Tarantino, LM, Rodriguez, LA, Reed, CL, McClearn, GE, Plomin, R & Erwin, VG 1999, 'Quantitative-trait loci analysis of cocaine-related behaviours and neurochemistry', Pharmacogenetics, vol. 9, no. 5, pp. 607-617.
Jones B, Tarantino LM, Rodriguez LA, Reed CL, McClearn GE, Plomin R et al. Quantitative-trait loci analysis of cocaine-related behaviours and neurochemistry. Pharmacogenetics. 1999;9(5):607-617.
Jones, Byron ; Tarantino, Lisa M. ; Rodriguez, Lawrence A. ; Reed, Cheryl L. ; McClearn, Gerald E. ; Plomin, Robert ; Erwin, V. Gene. / Quantitative-trait loci analysis of cocaine-related behaviours and neurochemistry. In: Pharmacogenetics. 1999 ; Vol. 9, No. 5. pp. 607-617.
@article{81ff6b1a4b634c4e89232efd146b5d02,
title = "Quantitative-trait loci analysis of cocaine-related behaviours and neurochemistry",
abstract = "We recently conducted a dose-response study of the effects of cocaine on several activity measures in the panel of BxD/Ty recombinant inbred mice. Animals were tested in an automated activity chamber over 2 days with i.p. saline on day 1 and i.p. cocaine on day 2, at one of four doses, 5, 15, 30 or 45 mg kg-1. The monitor recorded total distance traveled, nosepokes in a holeboard, repeated movements and time spent by an individual in proximity to the centre of the apparatus. Dose-response curves for locomotor activation, i.e. the difference between cocaine and saline scores, showed that for all strains tested, scores increased 5-30 mg kg-1. With few exceptions, locomotor activity at 45 mg kg-1 was not significantly higher than that at 30 mg kg-1. Repeated movement scores showed patterns similar to locomotor activity and nosepokes tended to be progressively inhibited by increasing doses of cocaine. Recombinant inbred strain mean distributions for all behaviours and at all doses exhibited continuous, rather than discrete variation, thus providing evidence of multiple-gene effects on cocaine-related behaviours. Quantitative trait loci (QTL) analysis pointed to several chromosomal locations associated with variations in cocaine-related behaviours and some are either identical or close to QTL reported by others. In separate groups of animals, densities of dopamine D1, and D2 receptors and dopamine uptake transporters were measured in the medial prefrontal cortex, caudate-putamen, nucleus accumbens and ventral midbrain. In all areas, all measures showed distributions consistent with polygenic influence and were associated with QTL. Of particular interest was our finding of a large segment on chromosome 15, which is related to dopamine receptor densities and cocaine-related behaviours.",
author = "Byron Jones and Tarantino, {Lisa M.} and Rodriguez, {Lawrence A.} and Reed, {Cheryl L.} and McClearn, {Gerald E.} and Robert Plomin and Erwin, {V. Gene}",
year = "1999",
language = "English (US)",
volume = "9",
pages = "607--617",
journal = "Pharmacogenetics and Genomics",
issn = "1744-6872",
publisher = "Lippincott Williams and Wilkins",
number = "5",

}

TY - JOUR

T1 - Quantitative-trait loci analysis of cocaine-related behaviours and neurochemistry

AU - Jones, Byron

AU - Tarantino, Lisa M.

AU - Rodriguez, Lawrence A.

AU - Reed, Cheryl L.

AU - McClearn, Gerald E.

AU - Plomin, Robert

AU - Erwin, V. Gene

PY - 1999

Y1 - 1999

N2 - We recently conducted a dose-response study of the effects of cocaine on several activity measures in the panel of BxD/Ty recombinant inbred mice. Animals were tested in an automated activity chamber over 2 days with i.p. saline on day 1 and i.p. cocaine on day 2, at one of four doses, 5, 15, 30 or 45 mg kg-1. The monitor recorded total distance traveled, nosepokes in a holeboard, repeated movements and time spent by an individual in proximity to the centre of the apparatus. Dose-response curves for locomotor activation, i.e. the difference between cocaine and saline scores, showed that for all strains tested, scores increased 5-30 mg kg-1. With few exceptions, locomotor activity at 45 mg kg-1 was not significantly higher than that at 30 mg kg-1. Repeated movement scores showed patterns similar to locomotor activity and nosepokes tended to be progressively inhibited by increasing doses of cocaine. Recombinant inbred strain mean distributions for all behaviours and at all doses exhibited continuous, rather than discrete variation, thus providing evidence of multiple-gene effects on cocaine-related behaviours. Quantitative trait loci (QTL) analysis pointed to several chromosomal locations associated with variations in cocaine-related behaviours and some are either identical or close to QTL reported by others. In separate groups of animals, densities of dopamine D1, and D2 receptors and dopamine uptake transporters were measured in the medial prefrontal cortex, caudate-putamen, nucleus accumbens and ventral midbrain. In all areas, all measures showed distributions consistent with polygenic influence and were associated with QTL. Of particular interest was our finding of a large segment on chromosome 15, which is related to dopamine receptor densities and cocaine-related behaviours.

AB - We recently conducted a dose-response study of the effects of cocaine on several activity measures in the panel of BxD/Ty recombinant inbred mice. Animals were tested in an automated activity chamber over 2 days with i.p. saline on day 1 and i.p. cocaine on day 2, at one of four doses, 5, 15, 30 or 45 mg kg-1. The monitor recorded total distance traveled, nosepokes in a holeboard, repeated movements and time spent by an individual in proximity to the centre of the apparatus. Dose-response curves for locomotor activation, i.e. the difference between cocaine and saline scores, showed that for all strains tested, scores increased 5-30 mg kg-1. With few exceptions, locomotor activity at 45 mg kg-1 was not significantly higher than that at 30 mg kg-1. Repeated movement scores showed patterns similar to locomotor activity and nosepokes tended to be progressively inhibited by increasing doses of cocaine. Recombinant inbred strain mean distributions for all behaviours and at all doses exhibited continuous, rather than discrete variation, thus providing evidence of multiple-gene effects on cocaine-related behaviours. Quantitative trait loci (QTL) analysis pointed to several chromosomal locations associated with variations in cocaine-related behaviours and some are either identical or close to QTL reported by others. In separate groups of animals, densities of dopamine D1, and D2 receptors and dopamine uptake transporters were measured in the medial prefrontal cortex, caudate-putamen, nucleus accumbens and ventral midbrain. In all areas, all measures showed distributions consistent with polygenic influence and were associated with QTL. Of particular interest was our finding of a large segment on chromosome 15, which is related to dopamine receptor densities and cocaine-related behaviours.

UR - http://www.scopus.com/inward/record.url?scp=0032692852&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032692852&partnerID=8YFLogxK

M3 - Article

VL - 9

SP - 607

EP - 617

JO - Pharmacogenetics and Genomics

JF - Pharmacogenetics and Genomics

SN - 1744-6872

IS - 5

ER -