Lobelane decreases methamphetamine self-administration in rats.
Lobelane, a minor alkaloid of Lobelia inflata and a synthetic, des-oxy analog of lobeline, has good affinity for the vesicular monoamine transporter and the dopamine transporter. The current study examined the ability of lobelane to specifically decrease methamphetamine self-administration. Rats were trained on a fixed ratio 5 schedule of reinforcement to self-administer methamphetamine (0.05 mg/kg/infusion, i.v.) or to respond for sucrose pellets. Upon reaching stable responding, rats were pretreated with lobelane (0.1, 1, 3, 5.6, or 10 mg/kg, s.c.) or saline, 15 min prior to the operant session. To assess the effect of repeated lobelane on methamphetamine self-administration, rats were pretreated with lobelane (5.6 or 10 mg/kg, s.c.) for 7 sessions. Behavioral specificity was further investigated by assessing the effects of lobelane (0.1, 1, 3, 5, or 10 mg/kg, s.c.) or saline on locomotor activity. Within the dose range tested, lobelane dose-dependently decreased methamphetamine self-administration, while having no effect on sucrose-maintained responding. Locomotor activity was decreased following only the highest dose of lobelane (10 mg/kg). Across repeated pretreatments, tolerance developed to the effect of lobelane on methamphetamine self-administration, demonstrating that the ability of lobelane to specifically decrease methamphetamine self-administration is a transient effect. Thus, taken together, the results show that although lobelane interacts with the pharmacological targets believed to be responsible for its ability to decrease methamphetamine self-administration, removal of the oxygen functionalities from the lobeline molecule may have afforded a compound with an altered pharmacokinetic and/or pharmacodynamic profile.
Neugebauer
Nichole M
NM
Department of Psychology, University of Kentucky, Lexington, KY 40536, USA.
Harrod
Steven B
SB
Stairs
Dustin J
DJ
Crooks
Peter A
PA
Dwoskin
Linda P
LP
Bardo
Michael T
MT
D019969:Amphetamine-Related Disorders / Q000503:physiopathology / Q000517:prevention & control / Q000523:psychology; D000818:Animals; D000697:Central Nervous System Stimulants / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D007262:Infusions, Intravenous; D008120:Lobeline / Q000031:analogs & derivatives* / Q000494:pharmacology*; D008297:Male; D008694:Methamphetamine / Q000008:administration & dosage*; D015394:Molecular Structure; D009043:Motor Activity / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012646:Self Administration; D013395:Sucrose / Q000008:administration & dosage
D000697:Central Nervous System Stimulants; D008694:Methamphetamine; D013395:Sucrose; D008120:Lobeline