Aversion Versus Reward in Nicotine Reinforcement Circuits

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Aversion Versus Rewardin Nicotine
ReinforcementCircuits

• Steven R. Laviolette, Ph.D.
• Dept. of Neuroscience
• University of Pittsburgh

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Examining the Motivational Effects of Nicotine
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The Motivational Effects of Nicotine in the
Ventral Tegmental Area
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Biphasic Motivational Effects of Nicotine in the
Ventral Tegmental Area
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Questions

• What neuroanatomical and pharmacological systems
  mediate the biphasic motivational effects of
  nicotine?
• Can these systems be dissociated?
• Functional interactions?
• The role of Dopamine?

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Dopamine Blockade Does Not Affect Nicotines
Discriminative Properties
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Nicotines 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
  Nicotines Rewarding Properties and Switches the
  Motivational Valence of Nicotine from Aversive to
  Rewarding

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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

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NMDA PPT Lesions
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The Effects of PPT Lesions on Nicotines
Motivational Effects
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The Acute Effects of Nicotine in the Ventral
Tegmental Area
VTA
Nicotine
PPT
GABA
Acute Nicotine
Reward Signal
Acute Nicotine
NAcc
DA
Aversion Signal
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Chronic Effects of Nicotine in the VTA
VTA
Nicotine
PPT
GABA
Desensitized
Reward Signal
DA
NAcc
Nicotine Craving
Withdrawal
Drug Seeking
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Functional Interactions Between Nicotine Reward
and Aversion Circuits
PFC
glutamate
VTA
Nicotine
a7
PPT
a7
Acute Reward
NMDA
GABA
a4b2
a7
glutamate
NMDA
DA
NAcc
a4b2
Acute Aversion
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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?

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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.