Lobelane decreases methamphetamine self-administration in rats

Nichole M. Neugebauer, Steven B. Harrod, Dustin Stairs, Peter A. Crooks, Linda P. Dwoskin, Michael T. Bardo

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)33-38
Number of pages6
JournalEuropean Journal of Pharmacology
Volume571
Issue number1
DOIs
StatePublished - Sep 24 2007

Fingerprint

Self Administration
Methamphetamine
Aptitude
Lobeline
Locomotion
Sucrose
Lobelia
lobelane
Vesicular Monoamine Transport Proteins
Reinforcement Schedule
Dopamine Plasma Membrane Transport Proteins
Alkaloids
Pharmacokinetics
Pharmacology
Oxygen

All Science Journal Classification (ASJC) codes

  • Cellular and Molecular Neuroscience
  • Pharmacology

Cite this

Neugebauer, N. M., Harrod, S. B., Stairs, D., Crooks, P. A., Dwoskin, L. P., & Bardo, M. T. (2007). Lobelane decreases methamphetamine self-administration in rats. European Journal of Pharmacology, 571(1), 33-38. https://doi.org/10.1016/j.ejphar.2007.06.003

Lobelane decreases methamphetamine self-administration in rats. / Neugebauer, Nichole M.; Harrod, Steven B.; Stairs, Dustin; Crooks, Peter A.; Dwoskin, Linda P.; Bardo, Michael T.

In: European Journal of Pharmacology, Vol. 571, No. 1, 24.09.2007, p. 33-38.

Research output: Contribution to journalArticle

Neugebauer, NM, Harrod, SB, Stairs, D, Crooks, PA, Dwoskin, LP & Bardo, MT 2007, 'Lobelane decreases methamphetamine self-administration in rats', European Journal of Pharmacology, vol. 571, no. 1, pp. 33-38. https://doi.org/10.1016/j.ejphar.2007.06.003
Neugebauer, Nichole M. ; Harrod, Steven B. ; Stairs, Dustin ; Crooks, Peter A. ; Dwoskin, Linda P. ; Bardo, Michael T. / Lobelane decreases methamphetamine self-administration in rats. In: European Journal of Pharmacology. 2007 ; Vol. 571, No. 1. pp. 33-38.
@article{3f620897d01249829893b89392e2e718,
title = "Lobelane decreases methamphetamine self-administration in rats",
abstract = "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.",
author = "Neugebauer, {Nichole M.} and Harrod, {Steven B.} and Dustin Stairs and Crooks, {Peter A.} and Dwoskin, {Linda P.} and Bardo, {Michael T.}",
year = "2007",
month = "9",
day = "24",
doi = "10.1016/j.ejphar.2007.06.003",
language = "English",
volume = "571",
pages = "33--38",
journal = "European Journal of Pharmacology",
issn = "0014-2999",
publisher = "Elsevier",
number = "1",

}

TY - JOUR

T1 - Lobelane decreases methamphetamine self-administration in rats

AU - Neugebauer, Nichole M.

AU - Harrod, Steven B.

AU - Stairs, Dustin

AU - Crooks, Peter A.

AU - Dwoskin, Linda P.

AU - Bardo, Michael T.

PY - 2007/9/24

Y1 - 2007/9/24

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=34548030024&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34548030024&partnerID=8YFLogxK

U2 - 10.1016/j.ejphar.2007.06.003

DO - 10.1016/j.ejphar.2007.06.003

M3 - Article

C2 - 17612524

AN - SCOPUS:34548030024

VL - 571

SP - 33

EP - 38

JO - European Journal of Pharmacology

JF - European Journal of Pharmacology

SN - 0014-2999

IS - 1

ER -