| First Author | Koeltzow TE | Year | 1998 |
| Journal | J Neurosci | Volume | 18 |
| Issue | 6 | Pages | 2231-8 |
| PubMed ID | 9482807 | Mgi Jnum | J:46772 |
| Mgi Id | MGI:1202050 | Doi | 10.1523/JNEUROSCI.18-06-02231.1998 |
| Citation | Koeltzow TE, et al. (1998) Alterations in dopamine release but not dopamine autoreceptor function in dopamine D3 receptor mutant mice. J Neurosci 18(6):2231-8 |
| abstractText | Dopamine (DA) autoreceptors expressed along the somatodendritic extent of midbrain DA neurons modulate impulse activity, whereas those expressed at DA nerve terminals regulate both DA synthesis and release. Considerable evidence has indicated that these DA autoreceptors are of the D-2 subtype of DA receptors. However, many pharmacological studies have suggested an autoreceptor role for the DA D-3 receptor. This possibility was tested with mice lacking the D-3 receptor as a result of gene targeting. The basal firing rates of DA neurons within both the substantia nigra and ventral tegmental area were not different in D-3 receptor mutant and wild-type mice. The putative D-3 receptor-selective agonist R(+)-trans-3,4,4a,10b-tetrahydro-4-propyl-2H,5H- (1)benzopyrano(4,3-b)-1,4-oxazin-9-ol (PD 128907) was equipotent at inhibiting the activity of both populations of midbrain DA neurons in the two groups of mice. In the gamma-butyrolactone (GEL) model of DA autoreceptor function, mutant and wild-type mice were identical with respect to striatal DA synthesis and its suppression by PD 128907. In vivo microdialysis studies of DA release in ventral strictum revealed higher basal levels of extracellular DA in mutant mice but similar inhibitory effects of PD 128907 in mutant and wildtype mice. These results suggest that the effects of PD 128907 on dopamine cell function reflect stimulation of D-2 as opposed to D-3 receptors. Although D-3 receptors do not seem to be significantly involved in DA autoreceptor function, they may participate in postsynaptically activated short-loop feedback modulation of DA release. |
