Orphanin FQ/nociceptin (NOC) has been reported to regulate dopaminergic neurotransmission in rewarding pathway, and to suppress the development of conditioned place preference (CPP) induced by certain addictive drugs. In this study, we investigated the effect of NOC on CPP induced by repeated administration of methamphetamine (MAP) in rats. Repeated administration of MAP (1 mg/kg, i.p.) induced substantial CPP. MAP-induced CPP was completely suppressed by NOC (10 nmol, i.c.v.). Pretreatment with [Nphe1]nociceptin(1-13)NH2 (50 nmol, i.c.v.), an antagonist of the NOC receptor, antagonized the suppressive effect of NOC on MAP-induced CPP. These results suggest that NOC blocks MAP-induced CPP by activation of the NOC receptor.

The mechanism of stimulation of noradrenaline (NA) release by nicotine (NIC) was investigated in human cerebral cortex slices preloaded with [3H]‐noradrenaline. NIC (10–1000 μM) increased [3H]‐NA release in a concentration‐dependent manner. NIC (100 μM)‐evoked [3H]‐NA release was largely dependent on external Ca2+, and was attenuated by ω‐conotoxin GVIA (0.1 μM) but not by nitrendipine (1 μM). Tetrodotoxin (1 μM) and nisoxetine (0.1 μM) attenuated the NIC (100 μM)‐evoked release of [3H]‐NA. Mecamylamine (10 μM), dihydro‐β‐erythroidine (10 μM) and d‐tubocurarine (30 μM), but not α‐bungarotoxin (α‐BTX, 0.1 μM), attenuated the NIC (100 μM)‐evoked release of [3H]‐NA. NIC (100 μM)‐evoked release of [3H]‐NA was not affected by 6‐cyano‐7‐nitroquinoxaline‐2,3‐dione (CNQX, 30 μM) and D(−)‐2‐amino‐5‐phosphonopentanoic acid (D‐AP5, 100 μM), but attenuated by MK‐801 (10 μM). MK‐801 (0.1–1000 μM) displaced the specific binding of [3H]‐nisoxetine with Ki values of 91.2 μM. NIC (100, 300 and 1000 μM) did not induce [3H]‐D‐aspartate release in human cerebral cortex slices. NIC (100 μM)‐evoked release of [3H]‐NA was attenuated by 7‐nitroindazole (10 μM), NG‐nitro‐L‐arginine methyl ester HCl (L‐NAME, 30 μM), NG‐monomethyl‐L‐arginine acetate (L‐NMMA, 300 μM). [3H]‐NA release induced by NIC (100 μM) was attenuated by methylene blue (3 μM) and 1H‐[1,2,4]oxadiazole[4,3‐α]quinoxalin‐1‐one (ODQ, 10 μM), and enhanced by zaprinast (30 μM). In conclusion, NIC stimulates the release of [3H]‐NA through activation of α‐BTX‐insensitive nicotinic acetylcholine receptors in the human cerebral cortex slices and this action of NIC is associated with modulation of the NO/cGMP pathway. British Journal of Pharmacology (2002) 137, 1063–1070. doi: