Effect of a novel nicotinic receptor antagonist, N,N'-dodecane-1,12-diyl-bis-3-picolinium dibromide, on nicotine self-administration and hyperactivity in rats.
OBJECTIVE
Recent work has shown that the novel compound N,N'-dodecane-1,12-diyl-bis-3-picolinium dibromide (bPiDDB) may selectively block nicotinic acetylcholine receptors involved in regulating dopamine release. The current experiments examined the acute effect of bPiDDB on nicotine self-administration, sucrose-maintained responding, and nicotine-induced changes in acute and sensitized locomotor activity.


METHODS
Rats were first trained to respond for either nicotine (i.v.) or sucrose pellets using a standard two-lever operant conditioning procedure using a fixed ratio 5 schedule of reinforcement and were then pretreated with bPiDDB (0, 0.3, 1, or 3 mg kg(-1)) 15 min prior to the session. In separate experiments, rats were assessed for nicotine-induced changes in locomotor activity following pretreatment with bPiDDB (1 or 3 mg kg(-1)) or mecamylamine (1 mg kg(-1)); pretreatments were assessed with both acute and repeated nicotine (0.4 mg kg(-1)) treatment.


RESULTS
Results showed that bPiDDB dose-dependently decreased nicotine self-administration, but not sucrose-maintained responding. In the locomotor experiments, bPiDDB attenuated the hyperactivity produced by acute and repeated nicotine; however, this effect was not robust compared to mecamylamine. In contrast to mecamylamine, bPiDDB did not block the initial hypoactivity produced by acute nicotine.


CONCLUSIONS
Since bPiDDB decreased nicotine self-administration specifically, this novel nicotinic receptor antagonist may constitute a lead for the development of a clinically useful treatment for tobacco dependence.
Neugebauer
N M
NM
Department of Psychology, University of Kentucky, Lexington, KY 40506, USA.
Zhang
Z
Z
Crooks
P A
PA
Dwoskin
L P
LP
Bardo
M T
MT
D000818:Animals; D003216:Conditioning, Operant / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D007262:Infusions, Intravenous; D007279:Injections, Subcutaneous; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology; D009042:Motivation; D009043:Motor Activity / Q000187:drug effects*; D009538:Nicotine / Q000008:administration & dosage*; D018733:Nicotinic Antagonists / Q000494:pharmacology*; D010847:Picolines / Q000494:pharmacology*; D011292:Premedication; D051381:Rats; D017207:Rats, Sprague-Dawley; D012646:Self Administration; D013395:Sucrose / Q000008:administration & dosage
C513964:N,N'-dodecane-1,12-diyl-bis-3-picolinium dibromide; D018733:Nicotinic Antagonists; D010847:Picolines; D013395:Sucrose; D008464:Mecamylamine; D009538:Nicotine