The imidazoline receptor ligand 2-(2-benzofuranyl)-2-imidazoline is a dopamine-releasing agent in the rat striatum in vivo

2-BFI (2-(2-benzofuranyl)-2-imidazoline) is a prototypical I-2-imidazoline receptor ligand. In vivo, however, 2-BFI (1-20 mg/kg) decreased the synthes is of dopa/dopamine (DA) in rat striatum through mechanisms not related to interaction with I-2-imidazoline receptors or to inhibition of the enzyme m onoamine oxidase. The aim of this study was to unravel the mechanism underl ying this potent effect of 2-BFI in brain. In vitro 2-BFI showed very low a ffinity for D-2-dopamine receptors (K-i = 47 muM), and in vivo the drug (7 mg/kg) decreased the synthesis of striatal dopa/DA similarly in control rat s (43%) and in rats pre-treated with alpha -methyl-para-tyrosine (50%) or c ocaine (51%), indicating that this effect was not the result of D-2-dopamin e autoreceptor direct stimulation, inhibition of the enzyme tyrosine hydrox ylase or blockade of neuronal DA reuptake. In DA-depleted (reserpine-treate d) rats, however, 2-BFI did not inhibit significantly (11%), the synthesis of dopa/DA in the striatum, indicating that the effect of 2-BFI was indirec tly mediated by endogenous DA th rough the activation of D-2-dopamine autor eceptors. In conclusion, the I-2-imidazoline receptor ligand 2-BFI is also a DA releasing agent in brain, and consequently a DA indirect agonist in vi vo. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.