Striatal D3 Receptor Research Articles

Neurobiological and Pharmacological Perspectives of D3 Receptors in Parkinson's Disease.

The discovery of the D3 receptor (D3R) subtypes of dopamine (DA) has generated an understandable increase in interest in the field of neurological diseases, especially Parkinson’s disease (PD). Indeed, although DA replacement therapy with l-DOPA has provided an effective treatment for patients with PD, it is responsible for invalidating abnormal involuntary movements, known as L-DOPA-induced dyskinesia, which constitutes a serious limitation of the use of this therapy. Of particular interest is the finding that chronic l-DOPA treatment can trigger the expression of D1R–D3R heteromeric interactions in the dorsal striatum. The D3R is expressed in various tissues of the central nervous system, including the striatum. Compelling research has focused on striatal D3Rs in the context of PD and motor side effects, including dyskinesia, occurring with DA replacement therapy. Therefore, this review will briefly describe the basal ganglia (BG) and the DA transmission within these brain regions, before going into more detail with regard to the role of D3Rs in PD and their participation in the current treatments. Numerous studies have also highlighted specific interactions between D1Rs and D3Rs that could promote dyskinesia. Finally, this review will also address the possibility that D3Rs located outside of the BG may mediate some of the effects of DA replacement therapy.

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.