PMID- 10591541
OWN - NLM
STAT- MEDLINE
DCOM- 20000106
LR  - 20131121
IS  - 0960-314X (Print)
IS  - 0960-314X (Linking)
VI  - 9
IP  - 5
DP  - 1999 Oct
TI  - Quantitative-trait loci analysis of cocaine-related behaviours and
      neurochemistry.
PG  - 607-17
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.
FAU - Jones, B C
AU  - Jones BC
AD  - Department of Biobehavioral Health, The Pennsylvania State University, University
      Park 16802-6508, USA.
FAU - Tarantino, L M
AU  - Tarantino LM
FAU - Rodriguez, L A
AU  - Rodriguez LA
FAU - Reed, C L
AU  - Reed CL
FAU - McClearn, G E
AU  - McClearn GE
FAU - Plomin, R
AU  - Plomin R
FAU - Erwin, V G
AU  - Erwin VG
LA  - eng
GR  - AA08125/AA/NIAAA NIH HHS/United States
GR  - AA08454/AA/NIAAA NIH HHS/United States
GR  - DA07171/DA/NIDA NIH HHS/United States
GR  - etc.
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Pharmacogenetics
JT  - Pharmacogenetics
JID - 9211735
RN  - 0 (Receptors, Dopamine)
RN  - I5Y540LHVR (Cocaine)
RN  - VTD58H1Z2X (Dopamine)
SB  - IM
MH  - Animals
MH  - Behavior, Animal/drug effects
MH  - Brain/metabolism
MH  - Chromosome Mapping
MH  - Cocaine/toxicity
MH  - Cocaine-Related Disorders/*genetics/metabolism/*psychology
MH  - Dopamine/metabolism
MH  - Female
MH  - Locomotion/drug effects
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Inbred DBA
MH  - Pharmacogenetics
MH  - *Quantitative Trait, Heritable
MH  - Receptors, Dopamine/genetics/metabolism
MH  - Recombination, Genetic
EDAT- 1999/12/11 00:00
MHDA- 1999/12/11 00:01
CRDT- 1999/12/11 00:00
PHST- 1999/12/11 00:00 [pubmed]
PHST- 1999/12/11 00:01 [medline]
PHST- 1999/12/11 00:00 [entrez]
PST - ppublish
SO  - Pharmacogenetics. 1999 Oct;9(5):607-17.