REPEATED INTRAVENOUS COCAINE ADMINISTRATION - LOCOMOTOR-ACTIVITY AND DOPAMINE D-2 D-3 RECEPTORS/

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.