title: A novel highly selective 5-HT6 receptor antagonist attenuates ethanol and nicotine seeking but does not affect inhibitory response control in Wistar rats.
abstract: Recent studies suggest a potential role for 5-hydroxytryptamine(6) (5-HT(6)) receptors in the regulation of addictive behavior. In the present study, our aim was to investigate whether the novel highly selective 5-HT(6) receptor antagonist compound (CMP) 42 affected nicotine and ethanol seeking behavior in Wistar rats. We have also studied whether CMP 42 had beneficial effects in a model of impulse control, as measured in the 5-choice serial reaction time task (5-CSRTT). Rats were trained to nose poke to receive intravenous infusions of nicotine or an ethanol drop. CMP 42 (3-30 mg/kg intraperitoneally, i.p.) was administered to investigate the effects on nicotine self-administration. Rats were also tested for cue-induced reinstatement of nicotine and ethanol seeking. In addition, the effects of CMP 42 were studied on the number of anticipatory responses in the 5-CSRTT. CMP 42 was effective in reducing nicotine self-administration and reinstatement of nicotine seeking at a dose of 30 mg/kg (i.p.). CMP 42 was also effective in reducing reinstatement of ethanol seeking (30 mg/kg i.p.). In contrast, CMP 42 did not affect anticipatory responding at doses tested, indicating no effects on impulse control. These results add to a body of evidence implicating the 5-HT(6) receptor as a viable target for the control of drug abuse. Specifically, we demonstrated for the first time effects on nicotine self-administration and on nicotine and ethanol reinstatement. Further, these effects are probably not mediated by effects on impulse control.
authors.affiliation: Abbott Healthcare Products BV (Formerly Solvay Pharmaceuticals BV), C.J. van Houtenlaan 36, 1381 CP Weesp, The Netherlands. Electronic address: Natasja.Debruin@ime.fraunhofer.de.
authors.forename: N M W J
authors.initials: NMWJ
authors.lastname: de Bruin
authors.affiliation: Abbott Healthcare Products BV (Formerly Solvay Pharmaceuticals BV), C.J. van Houtenlaan 36, 1381 CP Weesp, The Netherlands.
authors.forename: A C
authors.initials: AC
authors.lastname: McCreary
authors.affiliation: Abbott Healthcare Products BV (Formerly Solvay Pharmaceuticals BV), C.J. van Houtenlaan 36, 1381 CP Weesp, The Netherlands.
authors.forename: A
authors.initials: A
authors.lastname: van Loevezijn
authors.affiliation: Neuroscience Campus Amsterdam, Department of Anatomy and Neurosciences, VU University Medical Center, Van der Boechorststaat 7, 1081 BT Amsterdam, The Netherlands.
authors.forename: T J
authors.initials: TJ
authors.lastname: de Vries
authors.affiliation: Abbott Healthcare Products BV (Formerly Solvay Pharmaceuticals BV), C.J. van Houtenlaan 36, 1381 CP Weesp, The Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: Venhorst
authors.affiliation: Abbott Healthcare Products BV (Formerly Solvay Pharmaceuticals BV), C.J. van Houtenlaan 36, 1381 CP Weesp, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: van Drimmelen
authors.affiliation: Abbott Healthcare Products BV (Formerly Solvay Pharmaceuticals BV), C.J. van Houtenlaan 36, 1381 CP Weesp, The Netherlands; Swammerdam Institute of Life Sciences (SILS), University of Amsterdam, Sciencepark 904, 1098 XH Amsterdam, The Netherlands.
authors.forename: C G
authors.initials: CG
authors.lastname: Kruse
mesh_terms: D000428:Alcohol Drinking / Q000188:drug therapy* / Q000523:psychology; D000704:Analysis of Variance; D000818:Animals; D002492:Central Nervous System Depressants / Q000008:administration & dosage / Q000494:pharmacology; D003463:Cues; D003627:Data Interpretation, Statistical; D058999:Drug-Seeking Behavior / Q000187:drug effects*; D000431:Ethanol / Q000008:administration & dosage / Q000494:pharmacology; D005108:Extinction, Psychological / Q000187:drug effects; D007175:Impulsive Behavior / Q000188:drug therapy / Q000523:psychology; D007262:Infusions, Intravenous; D008297:Male; D009538:Nicotine / Q000008:administration & dosage / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000008:administration & dosage / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects; D011985:Receptors, Serotonin / Q000187:drug effects*; D012008:Recurrence; D012646:Self Administration; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013449:Sulfonamides / Q000494:pharmacology; D014029:Tobacco Use Disorder / Q000188:drug therapy* / Q000523:psychology
chemical_list: C580582:CMP 42; D002492:Central Nervous System Depressants; D018722:Nicotinic Agonists; D011720:Pyrazoles; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D013449:Sulfonamides; C097216:serotonin 6 receptor; D000431:Ethanol; D009538:Nicotine