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

Citation
Bc. Jones et al., Quantitative-trait loci analysis of cocaine-related behaviours and neurochemistry, PHARMACOGEN, 9(5), 1999, pp. 607-617
Citations number
36
Categorie Soggetti
Pharmacology & Toxicology
Journal title
PHARMACOGENETICS
ISSN journal
0960314X → ACNP
Volume
9
Issue
5
Year of publication
1999
Pages
607 - 617
Database
ISI
SICI code
0960-314X(199910)9:5<607:QLAOCB>2.0.ZU;2-7
Abstract
We recently conducted a dose-response study of the effects of cocaine on se veral activity measures in the panel of BxD/Ty recombinant inbred mice. Ani mals were tested in an automated activity chamber over 2 days with i.p. sal ine 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 activati on, 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, l ocomotor activity at 45 mg kg(-1) was not significantly higher than that at 30 mg kg(-1). Repeated movement scores showed patterns similar to locomoto r activity and nosepokes tended to be progressively inhibited by increasing doses of cocaine. Recombinant inbred strain mean distributions for all beh aviours and at all doses exhibited continuous, rather than discrete variati on, thus providing evidence of multiple-gene effects on cocaine-related beh aviours. Quantitative trait loci (QTL) analysis pointed to several chromoso mal locations associated with variations in cocaine-related behaviours and some are either identical or close to QTL reported by others. In separate g roups of animals, densities of dopamine D-1, and D-2 receptors and dopamine uptake transporters were measured in the medial prefrontal cortex, caudate -putamen, nucleus accumbens and ventral midbrain. In all areas, all measure s showed distributions consistent with polygenic influence and were associa ted 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. Pharmacogenetics 9:607-617 (C) 1999 Lippincott Williams & Wilkins.