Dr. Wallace et al., REPEATED INTRAVENOUS COCAINE ADMINISTRATION - LOCOMOTOR-ACTIVITY AND DOPAMINE D-2 D-3 RECEPTORS/, Synapse, 23(3), 1996, pp. 152-163
The dopamine D-3 receptor has been implicated as a possible mediator i
n the reinforcement or abuse of psychostimulants such as cocaine. The
present studies examined the effects of repeated (14 day) intravenous
cocaine administration (saline vehicle, 0.5, 1.0 and 3.0 mg/kg) on loc
omotor activity and dopamine D-2 and D-3 receptor density in the rat s
triatum and nucleus accumbens. Male Sprague-Dawley rats (n = 40) were
implanted with an intravenous access port and allowed to recover for 2
days. An additional group of naive rats was included to control for s
urgical/injection stress (n = 10). Following 2 days of habituation tri
als, total, peripheral and central activity (photocell interruptions)
data were collected during alternate daily 60-minute test sessions. Re
peated cocaine treatment resulted in a significant dose-dependent incr
ease in striatal D-3 receptors which was predicted by daily 60-minute
central locomotor activity. Conversely, D-3 receptors in the nucleus a
ccumbens exhibited a significant dose-dependent reduction which was pr
edicted by the initial 5 minutes of central locomotor activity observe
d on peak sensitization days (days 6, 8 and 10). Sensitization to the
locomotor stimulatory effects of cocaine was dose-dependent, with the
time to peak sensitization day following the rank order of 0.5 > 1.0 >
3.0 mg/kg. The density of D-2 receptors in the striatum and nucleus a
ccumbens was unchanged by cocaine administration. These data suggest s
triatal and nucleus accumbens D-3 receptor involvement in the expressi
on of cocaine-induced behavioral sensitization. Thus, the D-3 receptor
s in the striatum and nucleus accumbens may be differentially involved
in the locomotor stimulation (striatal D-3) and reinforcing aspects (
nucleus accumbens D-3) of repeated cocaine administration. (C) 1996 Wi
ley-Liss, Inc.