Animal experiment:

Mice[3]AC5-/- mice are backcrossed to the C57BL/6J strain for 9 or 10 generations to obtain heterozygote N9 or N10 mice. Mice are treated with (+)-Dihydrexidine (30 mg/kg, i.p.)[3].

(+)-Dihydrexidine hydrochloride ((+)-DAR-0100 hydrochloride) is a dopamine D1 receptor agonist with an EC50 of 72± 21 nM.

(+)-Dihydrexidine hydrochloride (DHX) is a high-potency, bioavailable D1 dopamine receptor agonist. (+)-Dihydrexidine is screened for activity against 40 other binding sites, and is inactive (IC50 greater than 10 microM) against all except D2 dopamine receptors (IC50=130 nM) and alpha 2 adrenoreceptors (IC50=230 nM). Dihydrexidine competes stereoselectively and potently for D1 binding sites in rat striatal membranes labeled with [3H]SCH23390 with an IC50 of about 10 nM compared to about 30 nM for the prototypical D1 agonist SKF38393[2].

To examine the functional state of striatal neurons in response to D1 receptor activation, AC5+/+ and AC5-/- mice are injected with the D1 agonist (+)-Dihydrexidine (30 mg/kg, i.p.) and obtained the dorso-lateral striatum and NAc, separately, 45 min later for RT-PCR analysis. These experiments reveal that (+)-Dihydrexidine -triggered induction of the immediate early genes, c-fos, egr-1, and junB, in the NAc is markedly enhanced in AC5-/- mice compared with that in AC5+/+ mice, while the induction in the dorso-lateral striatum is suppressed in AC5-/- mice[3].

References:
[1]. Lewis MM, et al. Homologous desensitization of the D1A dopamine receptor: efficacy in causing desensitizationdissociates from both receptor occupancy and functional potency. J Pharmacol Exp Ther. 1998 Jul;286(1):345-53.
[2]. Mottola DM, et al. Dihydrexidine, a novel full efficacy D1 dopamine receptor agonist. J Pharmacol Exp Ther. 1992 Jul;262(1):383-93.
[3]. Kim KS, et al. Adenylyl cyclase-5 activity in the nucleus accumbens regulates anxiety-related behavior. J Neurochem. 2008 Oct;107(1):105-15.