The addition of five minor tobacco alkaloids increases nicotine-induced hyperactivity, sensitization and intravenous self-administration in rats.
Int. J. Neuropsychopharm.. 2009-04-15; 12(10): 1355
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1. Int J Neuropsychopharmacol. 2009 Nov;12(10):1355-66. doi:
10.1017/S1461145709000273. Epub 2009 Apr 15.
The addition of five minor tobacco alkaloids increases nicotine-induced
hyperactivity, sensitization and intravenous self-administration in rats.
Clemens KJ(1), Caillé S, Stinus L, Cador M.
(1)CNRS UMR 5227, Team Neuropsychopharmacology of Addiction, University of
Bordeaux 1 and 2, Bordeaux, France.
Several minor tobacco alkaloids have been found to exhibit properties
pharmacologically relevant to the addictive profile of tobacco; however, little
is known of their effects on a behavioural model of drug addiction. In this study
we compared the locomotor and reinforcing effects of intravenous nicotine (30
microg/kg per infusion) vs. a cocktail of nicotine plus five minor alkaloids
found in tobacco smoke (anabasine, nornicotine, anatabine, cotinine and
myosmine). Rats were initially tested for their locomotor response to nicotine or
nicotine plus the minor alkaloids with six intravenous injections over 1 h. We
then assessed the spontaneous acquisition of intravenous self-administration with
nicotine or nicotine plus the minor alkaloids, under a fixed-ratio 1 schedule
followed by responding on a fixed-ratio 5 schedule, progressive-ratio schedule
and a single within-session ascending dose-response test. The activity test was
repeated following the progressive-ratio phase to assess locomotor sensitization.
A second group of rats were then tested on the locomotor procedure to better
clarify the role of each individual minor alkaloid in nicotine-induced locomotor
activity. Compared to nicotine alone, addition of the minor tobacco alkaloids
increased locomotor activity and increased locomotor sensitization following
self-administration. During fixed-ratio 5, progressive ratio and the
dose-response test, rats receiving nicotine plus the minor alkaloids responded
significantly more than those receiving nicotine alone. Testing of each minor
alkaloid in the second experiment indicated that anatabine, cotinine and myosmine
individually increased nicotine-induced locomotor activity. These results suggest
that the minor tobacco alkaloids, particularly anatabine, cotinine and myosmine,
may increase the motivation for nicotine and thus facilitate smoking behaviour.
PMID: 19366487 [Indexed for MEDLINE]