Repeated intravenous cocaine administration: Locomotor activity and dopamine D₂/D₃ receptors

The dopamine D₃ receptor has been implicated as a possible mediator in 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 locomotor activity and dopamine D₂ and D₃ receptor density in the rat striatum 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 surgical/injection stress (n = 10). Following 2 days of habituation trials, total, peripheral and central activity (photocell interruptions) data were collected during alternate daily 60-minute test sessions. Repeated cocaine treatment resulted in a significant dose-dependent increase in striatal D₃ receptors which was predicted by daily 60-minute central locomotor activity. Conversely, D₃ receptors in the nucleus accumbens exhibited a significant dose-dependent reduction which was predicted by the initial 5 minutes of central locomotor activity observed 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 D₂ receptors in the striatum and nucleus accumbens was unchanged by cocaine administration. These data suggest striatal and nucleus accumbens D₃ receptor involvement in the expression of cocaine-induced behavioral sensitization. Thus, the D₃ receptors in the striatum and nucleus accumbens may be differentially involved in the locomotor stimulation (striatal D₃) and reinforcing aspects (nucleus accumbens D₃) of repeated cocaine administration.