Lobeline attenuates locomotor stimulation induced by repeated nicotine administration in rats

Dennis K. Miller, Steven B. Harrod, Thomas A. Green, Mei Yee Wong, Michael T. Bardo, Linda P. Dwoskin

Research output: Contribution to journalArticlepeer-review

49 Scopus citations

Abstract

Lobeline inhibits [3H]nicotine binding to rat brain membranes and nicotine-induced [3H]dopamine release from superfused rat striatal slices, indicating that lobeline acts as a nicotinic receptor antagonist. To determine whether lobeline also inhibits the effects of nicotine in vivo, the present study assessed the effect of lobeline pretreatment on nicotine-induced hyperactivity and sensitization. For 12 consecutive days, rats were injected subcutaneously with lobeline (3 mg/kg) or saline, followed 10 min later by nicotine (0.3 mg/kg) or saline injection, and activity was monitored. To determine if lobeline inhibits induction of sensitization to nicotine, 1 or 28 days later, rats were pretreated with saline followed by nicotine or saline. Lobeline attenuated nicotine-induced hyperactivity when both drugs were administered repeatedly. Although an initial injection of lobeline produced hypoactivity, tolerance to this effect developed. Importantly, tolerance did not develop to the lobeline-induced attenuation of nicotine hyperactivity. Lobeline attenuated the induction of sensitization to nicotine 1 day, but not 28 days, after the cessation of lobeline treatment. These results demonstrate that systemic administration of lobeline attenuates the locomotor-activating effects of repeated nicotine injection and the sensitization to nicotine, consistent with lobeline inhibition of nicotinic receptors and/or neurotransmitter transporters.

Original languageEnglish
Pages (from-to)279-286
Number of pages8
JournalPharmacology Biochemistry and Behavior
Volume74
Issue number2
DOIs
StatePublished - Jan 2003

Bibliographical note

Funding Information:
This research was supported by grants from the National Institute of Health (DA00399 [L.P.D.], DA06018 [S.B.H.], DA06043 [D.K.M.], DA06093 [T.A.G.], and DA13519 [L.P.D., M.T.B.]) and the University of Kentucky Center on Drug and Alcohol Research (D.K.M.). For the purpose of full disclosure, patents on lobeline are owned by the University of Kentucky and a potential royalty stream (L.P.D.) may occur consistent with University of Kentucky policy.

Keywords

  • Behavioral sensitization
  • Lobeline
  • Locomotor activity
  • Nicotine
  • Rat

ASJC Scopus subject areas

  • Biochemistry
  • Toxicology
  • Pharmacology
  • Clinical Biochemistry
  • Biological Psychiatry
  • Behavioral Neuroscience

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