Effects on locomotor activity after local application of D3 preferring compounds in discrete areas of the rat brain

Abstract

Compounds showing an in vitro binding preference for the dopamine D3 vs. D2 receptors were tested for effects on locomotor activity after local application in the nucleus accumbens (N Acc) and the ventral tegmental area (VTA) of the rat brain. R-(+)-7-OH-DPAT, a dopamine D3 preferring agonist, inhibited spontaneous locomotor activity over a wide dose range after injection into the N Acc. A decrease in activity over a wide dose range was also seen after local application into the VTA of both R-(+)-7-OH-DPAT and the dopamine D2 preferring agonist (+)-3-PPP. Furthermore, (+)-3-PPP produced a dose dependent increase in activity after local application into the N Acc. The putative D3 antagonist, U99194A, with a 30 fold preference for the dopamine D3 vs. D2 receptor, produced an increase in activity when injected into the N Acc. A similar pattern were seen after infusion into the lateral ventricle. Local application into the VTA did, however, not produce any significant effects. The present results support the hypothesis that dopamine D3 receptors (in contrast to the D2 receptors) are mainly postsynaptically located where they display an inhibitory action on locomotor activity.

Administration of the D2 Dopamine Receptor Antagonist Sulpiride into the Shell, but not the Core, of the Nucleus Accumbens Attenuates Cocaine Priming-Induced Reinstatement of Drug Seeking

“…One possible explanation for the discrepancy between these findings and those of Vorel et al (2002) could reside with the higher selectivity of SB-277011 as compared to U99194A for D3 vs D2 dopamine receptors (Kling-Petersen et al, 1995;Reavill et al, 2000;Vallone et al, 2000). Another possibility is that D3 receptor mechanisms acting at neuronal sites outside of the nucleus accumbens contribute to cocaine reinstatement.…”

“…D3 receptors have a 70-fold greater affinity for dopamine than any other dopamine receptor (Richtand et al, 2001). Sulpiride is approximately 100-fold more selective for the D2 vs D3 dopamine receptor subtype (Vallone et al, 2000), while the D3 antagonist used in these experiments, U99194A, has 30-fold preference for D3 vs D2 dopamine receptors (Kling-Petersen et al, 1995;Vallone et al, 2000). In contrast, little is known about the extent of L-750,667's behavioral effects.…”

“…L-750,667 (Sigma-Aldrich, St Louis, MO) was dissolved in distilled water. The doses of sulpiride (Phillips et al, 1994a, c;Baker et al, 1996) and U99194A (Kling-Petersen et al, 1995) were chosen based on previous investigations of intra-accumbal injections in comparable behavioral paradigms, as well as on the basis of optimizing efficacy at the D3 vs D2 receptor. D3 receptors have a 70-fold greater affinity for dopamine than any other dopamine receptor (Richtand et al, 2001).…”

Dose–response analysis of locomotor activity and stereotypy in dopamine D3 receptor mutant mice following acute amphetamine

“…Dopaminergic signaling in these pathways is mediated by G protein-coupled receptors grouped into two subfamilies: D1-like (D1 and D5) and D2-like (D2, D3, and D4) (reviewed in Missale et al, 1998). Accumulating evidence from pharmacological studies suggest that D3R stimulation is inhibitory to spontaneous and psychostimulant-induced locomotion, in opposition to concurrent D1R-and D2R-mediated signaling (Carr et al, 2002;De Boer et al, 1997;Ekman et al, 1998;Kling-Petersen et al, 1995;Ouagazzal and Creese, 2000;Pritchard et al, 2003;Waters et al, 1993;Xu et al, 1997;Zhang et al, 2004). A clear understanding of D3R behavioral functions has been limited, however, by the limited selectivity of D3R agonists and antagonists.…”

D3 dopamine receptor regulation of D5 receptor expression and function in renal proximal tubule cells

“…Rat RPT cells were treated with vehicle (dH 2 O), a D 3 receptor agonist (PD128907) (Sigma, St Louis, MO, USA) 21 or a D 3 receptor antagonist (U99194A, Sigma) 22 at the indicated concentrations and times. Immunoblotting was performed as previously reported, 20,23 except that the transblots were probed with the D 5 receptor (1 : 500; Research Genetics, Huntsville, AL, USA).…”