The aim of this study was to determine if 2-(2-benzofuranyl)-2-imidazoline (2-BFI) interacts with the opioid system in the rat locus coeruleus, using single-unit extracellular recordings.In morphine-dependent rats, acute administration of the selective imidazoline receptor ligands 2-BFI (10 and 40 mg kg−1, i.p. and 100 μg, i.c.v.) or valldemossine (10 mg kg−1, i.p.) did not modify the naloxone-induced hyperactivity of locus coeruleus neurons compared with that observed in the morphine-dependent control group.After chronic administration of 2-BFI (10 mg kg−1, i.p., three times daily, for 5 days) and morphine, naloxone-induced hyperactivity and tolerance to morphine were attenuated. This effect was not observed when a lower dose of 2-BFI (1 mg kg−1, i.p.) or valldemossine (10 mg kg−1, i.p.) were used.Acute administration of 2-BFI (10 and 40 mg kg−1, i.p. and 100 μg, i.c.v.) but not valldemossine (40 mg kg−1, i.p.) diminished the potency of morphine to inhibit locus coeruleus neuron activity in vivo (ED50 values increased by 2.3, 2.9; and 3.1 fold respectively). Similarly, the potency of Met5-enkephalin to inhibit locus coeruleus neurons was decreased when 2-BFI (100 μM) was applied to rat brain slices (EC50 increased by 5.6; P