Lobeline attenuates locomotor stimulation induced by repeated nicotine administration in rats.
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.
Miller
Dennis K
DK
College of Pharmacy, University of Kentucky, Rose Street, Lexington, KY 40536-0082, USA.
Harrod
Steven B
SB
Green
Thomas A
TA
Wong
Mei-Yee
MY
Bardo
Michael T
MT
Dwoskin
Linda P
LP
D000818:Animals; D003216:Conditioning, Operant / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D008120:Lobeline / Q000494:pharmacology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D009538:Nicotine / Q000037:antagonists & inhibitors*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013268:Stimulation, Chemical
D018722:Nicotinic Agonists; D009538:Nicotine; D008120:Lobeline