Aversion Versus Rewardin Nicotine ReinforcementCircuits Steven R. Laviolette, Ph.D. Dept. of Neuroscience University of Pittsburgh
The Motivational Effects of Nicotine in the Ventral Tegmental Area
Biphasic Motivational Effects of Nicotine in the Ventral Tegmental Area
Questions • What neuroanatomical and pharmacological systems mediate the biphasic motivational effects of nicotine? • Can these systems be dissociated? • Functional interactions? • The role of Dopamine?
Dopamine Blockade Does Not Affect Nicotine’s Discriminative Properties
Nicotine’s Biphasic Motivational Effects in the VTA • The Rewarding Effects of Acute Nicotine do Not Require Dopamine • Dopamine is Necessary for the Acute Aversive Effects of Dopamine Demonstrated in Both the CPP and CTA Paradigms • Mesolimbic Dopamine Blockade Potentiates Nicotine’s Rewarding Properties and Switches the Motivational Valence of Nicotine from Aversive to Rewarding
Which Neural Circuits are Required for the Acute Nicotine Reward Signal? • The Brainstem Pedunculopontine Nucleus (PPT) both sends and receives input from the VTA • The PPT is Critical for the Acute Rewarding Effects of Various Stimuli Including Opiates, Food, Sucrose, Sex
The Acute Effects of Nicotine in the Ventral Tegmental Area VTA Nicotine PPT GABA Acute Nicotine Reward Signal Acute Nicotine NAcc DA Aversion Signal
Chronic Effects of Nicotine in the VTA VTA Nicotine PPT GABA Desensitized Reward Signal DA NAcc Nicotine Craving Withdrawal Drug Seeking
Functional Interactions Between Nicotine Reward and Aversion Circuits PFC glutamate VTA Nicotine a7 PPT Acute Reward a7 NMDA GABA a4b2 a7 glutamate NMDA DA NAcc a4b2 Acute Aversion
Summary • Nicotine is unique in that the rewarding and aversive motivational properties can be dissociated on several levels • We propose that the functional balance between these separate motivational pathways in the VTA may determine vulnerability to nicotine addiction in the acute stage • We are now exploring how nicotine dependence and withdrawal may alter the functional interplay between these separate neural circuits • Does nicotine dependence/withdrawal induce a motivational switching mechanism, similar to opiates, in the VTA?
Acknowledgements Centre for Addiction & Mental Health Toronto, Canada Dept of Anatomy & Cell Biology University of Toronto Derek van der Kooy Tania Alexson Bill Corrigall Kathy Coen Laurie Adamson Funded by C.I.H.R.