ECON 546 Lecture Notes - Lecture 25: Neuroplasticity, Threonine, Acamprosate

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Lecture 25: Substance Abuse II Monday, April 16, 2018
Dr. Emmanuel Darcq
Review
- Addiction is a brain disease characterized by compulsive behaviour, continued abuse of
drugs despite negative consequences, persistent changes in brain structure and function
- Substances of abuse “hijack” reward circuit  each substance of abuse hijacks the
reward circuit and increases dopamine levels in the striatum, which produces pleasure
oHeroin will indirectly regulate DA release
oStimulants directly (cocaine, amphetamine) directly change the level of DA
oCannabinoids act on CB1 receptors  direct increase of DA
oNictone acts on AchRs  direct increase of DA
Cycle Underlying Addiction
- Three recurring steps: binge and intoxication  withdrawal and negative affect 
preoccupation and anticipation
oEach step will activate specific neurobiologic networks
oBinge and intoxication: globus pallidus, thalamus, ventral striatum, dorsal
striatum
oWithdrawal and negative affect: amygdala, basal nucleus of stria terminalis
oPreoccupation and anticipation: OFC, ACC, HC
- Repetition of this cycle will lead to neuroadaptatiions and behavioural changes
Molecular Pathway and Neuroadaptation Underlying Substance of Abuse
- Synaptic changes linking environmental stimuli, drug effects, and reward learning in
drug dependence by altering several pathways such as:
oDopamine (reduced activity after excessive intake)
oGlutamates (reduced activity due to excessive intake0
oStress pathways (CRF) (promotes addiction)
oBDNS (protects against addiction)
omTORc1 (promotes addiction) by promoting change in the synapse
Dopamine Pathway
- Less dopamine release with each cycle of the addiction
- Impacts mood and normal activity
- Excessive intake of heroin/cocaine  less DA release, more DA transporter, less DA
receptor
Dopamine Pathway in Humans
- Study using PET to image D2 receptor availability
- People with low receptor levels found amphetamine pleasant while those with high
levels found amphetamine unpleasant
- Dopamine D2 receptors are decreased by addiction
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Document Summary

Addiction is a brain disease characterized by compulsive behaviour, continued abuse of drugs despite negative consequences, persistent changes in brain structure and function. Repetition of this cycle will lead to neuroadaptatiions and behavioural changes. Molecular pathway and neuroadaptation underlying substance of abuse. Less dopamine release with each cycle of the addiction. Excessive intake of heroin/cocaine less da release, more da transporter, less da receptor. Study using pet to image d2 receptor availability. People with low receptor levels found amphetamine pleasant while those with high levels found amphetamine unpleasant. Dopamine d2 receptors are decreased by addiction. Excessive and repeated use of substances of abuse shift the balance between the d1r and d2r signaling to a predominance of d1r stimulatory over d2r inhibitory signaling, which might facilitate compulsive intake (decrease of d2, increase of d1) Vulnerability: low receptor levels found amphetamines pleasant while those with high levels found it unpleasant.

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