PMID- 21730011
OWN - NLM
STAT- MEDLINE
DCOM- 20111122
LR  - 20211020
IS  - 1521-0103 (Electronic)
IS  - 0022-3565 (Print)
IS  - 0022-3565 (Linking)
VI  - 339
IP  - 1
DP  - 2011 Oct
TI  - Patterns of nicotinic receptor antagonism: nicotine discrimination studies.
PG  - 194-202
LID - 10.1124/jpet.111.182170 [doi]
AB  - Evaluation of the discriminative stimulus effects of drugs is a useful procedure 
      for identification of receptor mediation of in vivo drug effects. This assay can 
      be enhanced when the stimulus effects of different doses of agonist are 
      evaluated. In the present study, rats were trained to discriminate small or large 
      doses of nicotine from saline, and interactions of these effects with nicotinic 
      receptor antagonists and partial agonists were determined. The insurmountable 
      nicotine antagonist mecamylamine blocked both the discriminative stimulus and 
      response rate-reducing effects of nicotine but was less effective against the 
      large dose of nicotine. The alpha4beta2*-selective, competitive antagonist 
      dihydro-beta-erythrodine (DHbetaE) antagonized the discriminative stimulus effects of 
      both doses but was less effective against the larger training dose of nicotine. 
      Schild analyses of DHbetaE suggested that different nicotinic receptor populations 
      may be mediating the stimulus effects of large and small doses of nicotine. This 
      suggestion was supported by observations that the discriminative stimulus effects 
      of the partial agonist cytisine were more like those of the large dose than of 
      the small dose of nicotine and that cytisine antagonized the effects of only the 
      small nicotine dose. Varenicline produced nicotine-like effects in both training 
      dose groups but reduced the discriminative stimulus effects of intermediate doses 
      of nicotine in the group trained to the small dose of nicotine. Overall, these 
      results suggest that small doses of nicotine produce their stimulus effects via 
      alpha4beta2* nicotine receptors, whereas larger doses of nicotine recruit additional 
      nicotine receptor subtypes, as revealed by drug discrimination assays in rats.
FAU - Jutkiewicz, Emily M
AU  - Jutkiewicz EM
AD  - Department of Pharmacology, University of Michigan, Ann Arbor, Michigan 
      48109-5632, USA.
FAU - Brooks, Emily A
AU  - Brooks EA
FAU - Kynaston, Adam D
AU  - Kynaston AD
FAU - Rice, Kenner C
AU  - Rice KC
FAU - Woods, James H
AU  - Woods JH
LA  - eng
GR  - T32 DA007268/DA/NIDA NIH HHS/United States
GR  - ImNIH/Intramural NIH HHS/United States
GR  - T32-DA007268/DA/NIDA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, N.I.H., Intramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20110705
PL  - United States
TA  - J Pharmacol Exp Ther
JT  - The Journal of pharmacology and experimental therapeutics
JID - 0376362
RN  - 0 (Benzazepines)
RN  - 0 (Bridged Bicyclo Compounds, Heterocyclic)
RN  - 0 (Nicotinic Agonists)
RN  - 0 (Nicotinic Antagonists)
RN  - 0 (Pyridines)
RN  - 0 (Quinoxalines)
RN  - 0 (Receptors, Nicotinic)
RN  - 0 (nicotinic receptor alpha4beta2)
RN  - 23255-54-1 (Dihydro-beta-Erythroidine)
RN  - 6EE945D3OK (Mecamylamine)
RN  - 6M3C89ZY6R (Nicotine)
RN  - 8J337D1HZY (Cytosine)
RN  - M6K314F1XX (epibatidine)
RN  - W6HS99O8ZO (Varenicline)
SB  - IM
MH  - Animals
MH  - Benzazepines/pharmacology
MH  - Bridged Bicyclo Compounds, Heterocyclic/pharmacology
MH  - Cytosine/pharmacology
MH  - Data Interpretation, Statistical
MH  - Dihydro-beta-Erythroidine/pharmacology
MH  - Discrimination Learning/drug effects
MH  - Discrimination, Psychological/*drug effects
MH  - Dose-Response Relationship, Drug
MH  - Male
MH  - Mecamylamine/pharmacology
MH  - Nicotine/*pharmacology
MH  - Nicotinic Agonists/*pharmacology
MH  - Nicotinic Antagonists/*pharmacology
MH  - Pyridines/pharmacology
MH  - Quinoxalines/pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, Nicotinic/*drug effects
MH  - Varenicline
PMC - PMC3186295
EDAT- 2011/07/07 06:00
MHDA- 2011/12/13 00:00
PMCR- 2012/10/01
CRDT- 2011/07/07 06:00
PHST- 2011/07/07 06:00 [entrez]
PHST- 2011/07/07 06:00 [pubmed]
PHST- 2011/12/13 00:00 [medline]
PHST- 2012/10/01 00:00 [pmc-release]
AID - jpet.111.182170 [pii]
AID - 3715186 [pii]
AID - 10.1124/jpet.111.182170 [doi]
PST - ppublish
SO  - J Pharmacol Exp Ther. 2011 Oct;339(1):194-202. doi: 10.1124/jpet.111.182170. Epub 
      2011 Jul 5.