Lobeline attenuates locomotor stimulation induced by repeated nicotine administration in rats

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

Research output: Contribution to journalArticle

45 Citations (Scopus)

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

Fingerprint

Lobeline
Nicotine
Rats
Nicotinic Receptors
Injections
Neurotransmitter Transport Proteins
Nicotinic Antagonists
Corpus Striatum
Withholding Treatment

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Behavioral Neuroscience
  • Pharmacology

Cite this

Lobeline attenuates locomotor stimulation induced by repeated nicotine administration in rats. / Miller, Dennis K.; Harrod, Steven B.; Green, Thomas; Wong, Mei Yee; Bardo, Michael T.; Dwoskin, Linda P.

In: Pharmacology Biochemistry and Behavior, Vol. 74, No. 2, 01.2003, p. 279-286.

Research output: Contribution to journalArticle

Miller, Dennis K. ; Harrod, Steven B. ; Green, Thomas ; Wong, Mei Yee ; Bardo, Michael T. ; Dwoskin, Linda P. / Lobeline attenuates locomotor stimulation induced by repeated nicotine administration in rats. In: Pharmacology Biochemistry and Behavior. 2003 ; Vol. 74, No. 2. pp. 279-286.
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