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.
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University of Kentucky Medical Center, Department of Pharmacology, Lexington 40536-0084, USA.
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D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology*; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D004361:Drug Tolerance; D007275:Injections, Intravenous; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D009294:Narcotics / Q000008:administration & dosage / Q000494:pharmacology*; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000187:drug effects* / Q000378:metabolism; D050637:Receptors, Dopamine D3
D018765:Dopamine Uptake Inhibitors; C493595:Drd3 protein, rat; D009294:Narcotics; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D003042:Cocaine