Patterns of responding differentiate intravenous nicotine self-administration from responding for a visual stimulus in C57BL/6J mice.
BACKGROUND
Testing genetically engineered mice in a reliable nicotine self-administration procedure could provide important insights into the molecular mechanisms underlying nicotine reinforcement.


OBJECTIVE
We assessed operant responding for intravenous nicotine infusions in C57BL/6J male mice under a fixed-ratio 3 schedule of reinforcement in which a visual cue was contingently associated with drug delivery.


RESULTS
Acquisition, dose-response function, extinction, and cue-induced reinstatement of operant behavior were characterized. Low nicotine doses (0.001-0.06 mg/kg/infusion) elicited response rates similar to those supported by saline, whereas a higher dose (0.1 mg/kg/infusion) decreased responding. Using an identical procedure to assess cocaine self-administration in an independent group of mice yielded an inverted U-shaped dose-response curve. Other mice trained to respond exclusively for the visual stimulus earned a similar number of reinforcers as mice self-administering saline or low nicotine doses, although with a lower selectivity for the active lever and their response rates were sensitive to the discontinuation and resumption of cue light presentation. Finally, patterns of responding for nicotine, cocaine, or the visual stimulus alone were analyzed using frequency distributions of inter-response intervals and extended return maps. These analyses revealed unique properties of nicotine, which dose-dependently delayed the first response post-timeout and increased the regularity of lever pressing activity.


CONCLUSIONS
Nicotine did not enhance the reinforcing properties of the visual cue paired with drug delivery. Interestingly, however, patterns of responding could differentiate nicotine self-administration from responding for a visual stimulus or saline and indicated that nicotine functioned as a salient stimulus driving highly regular operant behavior.
Contet
Candice
C
Department of Psychiatry, Mail Code 0603, School of Medicine, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0603, USA.
Whisler
Kimberly N
KN
Jarrell
Holly
H
Kenny
Paul J
PJ
Markou
Athina
A
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003042:Cocaine / Q000008:administration & dosage; D003216:Conditioning, Operant / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009538:Nicotine / Q000008:administration & dosage* / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000008:administration & dosage* / Q000494:pharmacology; D012055:Reinforcement Schedule; D012646:Self Administration
D018722:Nicotinic Agonists; D009538:Nicotine; D003042:Cocaine