Gradient of dopamine responsiveness to dopamine receptor agonists in subregions of the rat nucleus accumbens.

The present study sought to investigate the possibility that the degree of selectivity of dopamine D3/D2 receptor agonists such as quinelorane, 7-hydroxy-2-dipropylaminotetralin (7-OH-DPAT), quinpirole and apomorphine on dopamine D3 over D2 receptor subtypes can be assessed by measuring dopamine transmission in the shell vs. core compartments of the nucleus accumbens by using microdialysis in freely moving rats. Significant reductions in dialysate dopamine levels compared to vehicle-treated animals were observed in the shell of the nucleus accumbens with 3, 10 and 30 microg/kg quinelorane, 100 microg/kg 7-OH DPAT, 25 and 100 microg/kg quinpirole, and 100 microg/kg apomorphine. In the core subregion, significant reductions in dopamine were seen at 10 and 30 microg/kg quinelorane, 25 and 100 microg/kg 7-OH-DPAT, 100 microg/kg quinpirole and 100 microg/kg apomorphine. However, a significant shell/core dichotomy could only be observed in response to the lowest dose of quinelorane (3 microg/kg) with the shell being hyper-responsive compared with the core. The present findings suggest that quinelorane is one of the most selective dopamine D3 receptor agonists based on its ability to target the shell subregion of the nucleus accumbens.