The Journal of Neuroscience, October 1, 2002, 22(19):8653-8660
Lesions of the Tegmental Pedunculopontine Nucleus Block the
Rewarding Effects and Reveal the Aversive Effects of Nicotine in the
Ventral Tegmental Area
Steven R.
Laviolette1,
Tania O.
Alexson2, and
Derek
van der Kooy1, 2
1 Neurobiology Research Group, Department of Anatomy
and Cell Biology, and 2 Institute of Medical Sciences,
University of Toronto, Toronto, Ontario, Canada M5S 1A8
Nicotine, the primary psychoactive component of tobacco smoke, is
known to possess potent rewarding and aversive stimulus properties. The
mammalian ventral tegmental area (VTA) is involved importantly in the
mediation of the motivational effects of nicotine. However, the neural
outputs from the VTA that may be involved in the transmission of the
rewarding and aversive motivational effects of nicotine are not well
understood. We report that bilateral lesions of the tegmental
pedunculopontine nucleus (TPP) double dissociate the rewarding and
aversive motivational effects of nicotine. Using a conditioned place
preference paradigm, bilateral TPP lesions blocked a nicotine reward
signal and revealed the aversive motivational properties of intra-VTA
nicotine. These same TPP lesions did not block an aversive nicotine
signal, as measured in a conditioned taste aversion paradigm. TPP
lesions also produce an attenuation in nicotine-induced locomotor
activity; however, neither learning nor performance deficits can
account for these observed effects, because TPP-lesioned animals still showed clear aversive nicotine conditioning in two separate behavioral paradigms. Our results suggest that the rewarding effects of nicotine in the VTA are dependent on a nondopaminergic, descending reward pathway to the brainstem TPP.
Key words:
ventral tegmental area; pedunculopontine tegmental
nucleus; nicotine; reward; addiction; aversion
Copyright © 2002 Society for Neuroscience 0270-6474/02/22198653-08$05.00/0