TABLE 1

Summary of results from nicotinic and nonnicotinic compounds studied in nicotine self-administration and drug discrimination

DrugMechanism of actionNicotine self-administrationNicotine discriminationReferences
Vareniclinepartial α4β2* nAChR agonist full α7 nAChR agonist↓ Nicotine SA in rats ↓ cue-induced reinstatement of nicotine SA in ratsFull substitution in mice, rats, monkeys; partial substitution with no antagonism in mice; partial substitution with antagonism in ratsRollema et al., 2007; LeSage et al., 2009; Jutkiewicz et al., 2011; Cunningham et al., 2012; Le Foll et al., 2012; Cunningham and McMahon, 2013; Moerke et al., 2017
BupropionDAT/NET reuptake inhibitorNo substitution in monkeys and rats; partial substitution in rats and mice; full substitution in ratsWiley et al., 2002; Young and Glennon, 2002; Desai et al., 2003; Shoaib et al., 2003; Damaj et al., 2010; Cunningham et al., 2012
AT-1001α3β4 nAChR partial agonist↓ Stress-induced reinstatement of nicotine SA in ratsYuan et al., 2017
Clonidineα2 adrenergic agonist↓ Footshock-induced reinstatement of nicotine SA in ratsZislis et al., 2007; Yamada and Bruijnzeel, 2011
NortriptylineNET/SERT reuptake inhibitor↓ Nicotine SA in rats (only at rate-suppressing doses)No substitution in ratsWing and Shoaib, 2012
PhysostigmineAChE inhibitorNo substitution in rats; partial substitution in ratsRosecrans and Meltzer, 1981; Pratt et al., 1983; Rosecrans, 1989; Giarola et al., 2011
DonepezilAChE inhibitor↓ Nicotine SA in ratsFull substitution in monkeysAshare et al., 2012; Kimmey et al., 2014; Moerke and McMahon, 2019
GalantamineAChE inhibitor↓ Nicotine SA in ratsFull substitution in monkeys; partial substitution in ratsGiarola et al., 2011; Hopkins et al., 2012; Liu, 2013; Moerke and McMahon, 2019
Atropinemuscarinic AChR antagonistNo antagonism in rats; antagonism in monkeys (but very large training dose)Rosecrans, 1989; Moerke and McMahon, 2019
HexamethoniumPeripherally restricted nAChR antagonistNo antagonism in rats (including i.c.v.)Hazell et al., 1978; Stolerman et al., 1984; Rosecrans, 1989; Besheer et al., 2004; Palmatier et al., 2004
ChlorisondaminePeripherally restricted nAChR antagonistNo antagonism in rats (systemic) persistent antagonism in rats (i.c.v.)Kumar et al., 1987; Stolerman et al., 1988
MecamylaminenAChR antagonist.Antagonism in mice, rats, monkeysMorrison and Stephenson, 1969; Stolerman et al., 1984, 1988, 1999; Besheer et al., 2004; Palmatier et al., 2004; Jutkiewicz et al., 2011; Cunningham et al., 2016; Moerke et al., 2017
PempidinenAChR antagonistAntagonism in ratsStolerman et al., 1988
DHβEβ2* nAChR-selective antagonistAntagonism in mice, rats, monkeysStolerman et al., 1997; Gommans et al., 2000; Shoaib et al., 2000; Moerke et al., 2017
MLAα7 nAChR antagonist↓ Nicotine SA in ratsNo antagonism in mice, rats, monkeys (including i.c.v.)Brioni et al., 1996; Gommans et al., 2000; Markou and Paterson, 2001; Zaniewska et al., 2006; Moerke et al., 2017
SB-334867hcrtR1 antagonist↓ Nicotine SA in rats ↓ cue-induced reinstatement of nicotine SA in rats no effect on footshock-induced reinstatement of nicotine SA in ratsHollander et al., 2008; LeSage et al., 2010; Plaza-Zabala et al., 2010, 2013
TCSOX229hcrtR2 antagonistNo attenuation of cue-induced reinstatement of nicotine SA in ratsPlaza-Zabala et al., 2013
2-SORAhcrtR2 antagonistNo effect nicotine SA in rats blocked cue-induced reinstatement of nicotine SA in rats no effect on nicotine-induced reinstatement of nicotine SA in ratsUslaner et al., 2014
AlmorexanthcrtR1/hcrtR2 antagonist↓ Nicotine SA in ratsLeSage et al., 2010
TCS1102hcrtR1/hcrtR2 antagonistNo effect on cue-induced reinstatement of nicotine SA in ratsKhoo et al., 2017

  • DAT, dopamine transporter; i.c.v., intracerebroventricular; NET, norepinephrine transporter; SERT, serotonin transporter.