PMID- 22189292
OWN - NLM
STAT- MEDLINE
DCOM- 20120720
LR  - 20220316
IS  - 1740-634X (Electronic)
IS  - 0893-133X (Print)
IS  - 0893-133X (Linking)
VI  - 37
IP  - 5
DP  - 2012 Apr
TI  - The 5-HT2C receptor agonist lorcaserin reduces nicotine self-administration, 
      discrimination, and reinstatement: relationship to feeding behavior and impulse 
      control.
PG  - 1177-91
LID - 10.1038/npp.2011.303 [doi]
AB  - Lorcaserin ((1R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine HCl) is a 
      selective 5-HT(2C) receptor agonist with clinical efficacy in phase-III obesity 
      trials. Based on evidence that this drug class also affects behaviors motivated 
      by drug reinforcement, we compared the effect of lorcaserin on behavior 
      maintained by food and nicotine reinforcement, as well as the stimulant and 
      discriminative stimulus properties of nicotine in the rat. Acutely administered 
      lorcaserin (0.3-3 mg/kg, subcutaneous (SC)) dose dependently reduced feeding 
      induced by 22-h food deprivation or palatability. Effects up to 1 mg/kg were 
      consistent with a specific effect on feeding motivation. Lorcaserin (0.6-1 mg/kg, 
      SC) reduced operant responding for food on progressive and fixed ratio schedules 
      of reinforcement. In this dose range lorcaserin also reversed the motor stimulant 
      effect of nicotine, reduced intravenous self-administration of nicotine, and 
      attenuated the nicotine cue in rats trained to discriminate nicotine from saline. 
      Lorcaserin also reduced the reinstatement of nicotine-seeking behavior elicited 
      by a compound cue comprising a nicotine prime and conditioned stimulus previously 
      paired with nicotine reinforcement. Lorcaserin did not reinstate nicotine-seeking 
      behavior or substitute for a nicotine cue. Finally, lorcaserin (0.3-1 mg/kg) 
      reduced nicotine-induced increases in anticipatory responding, a measure of 
      impulsive action, in rats performing the five-choice serial reaction time task. 
      Importantly, these results indicate that lorcaserin, and likely other selective 
      5-HT(2C) receptor agonists, similarly affect both food- and nicotine-motivated 
      behaviors, and nicotine-induced impulsivity. Collectively, these findings 
      highlight a therapeutic potential for 5-HT(2C) agonists such as lorcaserin beyond 
      obesity into addictive behaviors, such as nicotine dependence.
FAU - Higgins, Guy A
AU  - Higgins GA
AD  - InterVivo Solutions Inc., Toronto, ON, Canada. guyh@intervivo.com
FAU - Silenieks, Leo B
AU  - Silenieks LB
FAU - Rossmann, Anne
AU  - Rossmann A
FAU - Rizos, Zoe
AU  - Rizos Z
FAU - Noble, Kevin
AU  - Noble K
FAU - Soko, Ashlie D
AU  - Soko AD
FAU - Fletcher, Paul J
AU  - Fletcher PJ
LA  - eng
GR  - Canadian Institutes of Health Research/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20111221
PL  - England
TA  - Neuropsychopharmacology
JT  - Neuropsychopharmacology : official publication of the American College of 
      Neuropsychopharmacology
JID - 8904907
RN  - 0 (6-chloro-5-methyl-1-((2-(2-methylpyrid-3-yloxy)pyrid-5-yl)carbamoyl)indoline)
RN  - 0 (Aminopyridines)
RN  - 0 (Benzazepines)
RN  - 0 (Indoles)
RN  - 0 (Nicotinic Agonists)
RN  - 0 (Serotonin Receptor Agonists)
RN  - 637E494O0Z (lorcaserin)
RN  - 6M3C89ZY6R (Nicotine)
SB  - IM
MH  - Aminopyridines/pharmacology
MH  - Analysis of Variance
MH  - Animals
MH  - Behavior, Animal/drug effects
MH  - Benzazepines/*pharmacology
MH  - Choice Behavior/drug effects
MH  - Conditioning, Operant/*drug effects
MH  - Discrimination, Psychological/*drug effects
MH  - Dose-Response Relationship, Drug
MH  - Drug Administration Routes
MH  - Eating/drug effects
MH  - Feeding Behavior/drug effects
MH  - Impulsive Behavior/drug therapy
MH  - Indoles/pharmacology
MH  - Male
MH  - Motor Activity/drug effects
MH  - Nicotine/*administration & dosage
MH  - Nicotinic Agonists/*administration & dosage
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Reaction Time/drug effects
MH  - *Reinforcement, Psychology
MH  - Rotarod Performance Test
MH  - Self Administration
MH  - Serotonin Receptor Agonists/*pharmacology
PMC - PMC3306879
EDAT- 2011/12/23 06:00
MHDA- 2012/07/21 06:00
PMCR- 2013/04/01
CRDT- 2011/12/23 06:00
PHST- 2011/12/23 06:00 [entrez]
PHST- 2011/12/23 06:00 [pubmed]
PHST- 2012/07/21 06:00 [medline]
PHST- 2013/04/01 00:00 [pmc-release]
AID - npp2011303 [pii]
AID - 10.1038/npp.2011.303 [doi]
PST - ppublish
SO  - Neuropsychopharmacology. 2012 Apr;37(5):1177-91. doi: 10.1038/npp.2011.303. Epub 
      2011 Dec 21.