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.