Varenicline and cytisine: two nicotinic acetylcholine receptor ligands reduce ethanol intake in University of Chile bibulous rats.
BACKGROUND
Neuronal nicotinic acetylcholine receptors (nAChRs) are pharmacological targets that have recently been implicated in the reinforcing effects of many drugs of abuse, including ethanol. Varenicline and cytisine are nAChR partial agonists in clinical use as smoking cessation aids. However, their efficacies to reduce alcohol consumption have not been fully studied.


OBJECTIVE
This study aims to compare the effects of varenicline and cytisine on ethanol consumption by rats bred for many generations as high ethanol drinkers (UChB).


RESULTS
Repeated dosing (0.5 or 1.0 mg/kg/day i.p.) of varenicline or cytisine, for three consecutive days, to male UChB rats pre-exposed to 10 % (v/v) ethanol and water 24 h/day for 4 weeks, significantly reduced alcohol intake and preference of ethanol over water during 1- and 24-h ethanol access periods. This effect was specific for ethanol intake and was not observed for 0.2 % saccharin or water consumption. Varenicline appears to be more effective than cytisine, probably due to its more favorable pharmacokinetic and pharmacodynamic properties. Long-term use of both nAChRs ligands for more than 8-10 days induced tolerance to their effects on ethanol consumption.


CONCLUSIONS
This preclinical study in UChB rats demonstrated that both varenicline and cytisine reduce alcohol intake, with varenicline producing a greater and longer-lasting reduction than cytisine. However, dose adjustment will have to be considered as a possible way to counter tolerance arising after continued use.
Departamento de Fisiología, Facultad de Ciencias, Universidad de Valparaíso, Av. Gran Bretaña 1111, Playa Ancha, Valparaíso, Chile. ramon.sotomayor@uv.cl
Ramón
R
Sotomayor-Zárate
Katia
K
Gysling
Usoa E
UE
Busto
Bruce K
BK
Cassels
Lutske
L
Tampier
María Elena
ME
Quintanilla
D000428:Alcohol Drinking / Q000517:prevention & control*; D000470:Alkaloids / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001392:Azocines / Q000008:administration & dosage / Q000494:pharmacology; D001552:Benzazepines / Q000008:administration & dosage / Q000494:pharmacology*; D002677:Chile; D004305:Dose-Response Relationship, Drug; D004326:Drinking / Q000187:drug effects; D004334:Drug Administration Schedule; D000431:Ethanol / Q000008:administration & dosage*; D008297:Male; D018722:Nicotinic Agonists / Q000008:administration & dosage / Q000494:pharmacology; D011807:Quinolizines / Q000008:administration & dosage / Q000494:pharmacology; D011810:Quinoxalines / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D012439:Saccharin / Q000008:administration & dosage; D013997:Time Factors; D000068580:Varenicline; D000093843:Quinolizidine Alkaloids
D000470:Alkaloids; D001392:Azocines; D001552:Benzazepines; D000431:Ethanol; D018722:Nicotinic Agonists; D011807:Quinolizines; D011810:Quinoxalines; D012439:Saccharin; D000068580:Varenicline; C004712:cytisine; D000093843:Quinolizidine Alkaloids