Roles of Neurobiology in Redefining Treatment for Addiction - Eliot Lawrence Gardner PHD - ISAM 2013 - Kuala Lumper

Dr. Gardner has written more than 400 papers. Harvard University. Albert Einstein. Head of Neuroscience NIDA, Distinguished Science Scholar


Addiction - primary chronic disease of brain , reward, motivation, memory and related circuitry
What do we know of brain circuitry and is this knowledge helping in the treatment of addiction
Of 30 million chemicals known, only 100 are addictive,  humans and animals self administer
Pleasure reward system of brain - nucleus accumbens Medial Forebrain Bundle, VTA - reward; amygdalll - emotions; frontal and prefrontal - planning judgements
Know this by electrical brain stimulation reward in laboratory animals and in human patients

Animals will self administer - ecstatically euphorically pleasurable - electrical stimulation
Planting electrodes into reward circuitry of brain, surgically.  Electrodes inserted into various parts of the brain pleasure circuitry and studied doing tasks, can be done with monkeys and rats
Canula can be inserted in the animals so that lever presses can increase dosage
Stimulation frequency - stimulation response curves -- lever presses/30 sec
Shows left shift of dose response curve showing THC is very pleasurable, same in animal that clinic patient, 'high dose - good trip, low dose - bad trip'

Crucial reward circuitry is dopamine - know this by virtually all addictive drugs are DA agaonists, one common feature
Animal set up with IV cocaine and also a micro dialysis tubing to sample neurochemistry from brain during the self administry
eg Heroin - Dopamine in the extracellular space by pleasure centre of the brain - animals pattern can be seen with hit of cocaine and elevation of dopamine then as dopamine falls animal voluntarily self administers. They are self administering to titrate the dopamine and their pleasure
Catecholamine Synthesis Pathway - Blockade - stops electrical stimulation reward -


We have known since 1969 dopamine the reward
Proponent and Opponent -  giving morphine and tolerance increases - move the giving of morphine slightly and the effects are dysphoric
-patients tell us , after a while that they don't use heroin to get high, use to get straight, they enter a chronic dopamine deficiency state
Drug withdrawal processes  - shown with thc as example







"Reward deficiency is the driving force of addiction"
There is atrophy of the pleasure centres in those genetically bred for addiction potential and those who
have used drugs for a while

DA D3 receptor antagonists
Feeling good and well being are associated with dopamine
Social and dominant monkeys are high in dopamine whereas those who are subordinate and especially those alone have low dopamine.
Relationship of social rank to cocaine self administration - subordinate monkeys will use more cocaine, more at risk for drug abuse
227 days of abstinence the monkey is still at greater risk of using drugs with low dopamine
Reduced D2/D3 and impulsive animals
Cocaine self administered more in the impulsive aniamls

Medications that reverse drug seeking for pleasure to habit forming

Relapse - reuse trigger of drug, cues and stress

Stress trigger relapse circuits 2 in brain -
- leads to possibility of using CRF antagonists and Functional Noradrenaline Antagonists
presynaptic eg - clonidine

Increase relapse vulnerability over time - incubation of craving -
BDNF mediatied synaptic remodelling

What about Memory?
Maladaptive drug associated memories
disorder of aberrant learning
strong instrumental memories as persistent stimulus-response habits
interation between pavlovian and instrument learning
Memories related to addiction - hippocampus and amygdalla

Future of Addiction Th

erapy
-neurobiology driven
social therapies work but we need more
-predicting vulnerability to addiction by neuro-imaging - pre teens to get them in treatment before they
take the drug

Question and Answer
- what about spontaneous recovery and recovery in general, and those who grow out of it
Noted this true and can show in animals with PET scan , so question is to explain and identify those who can with research


(This was a truly gifted presentation of basic science and research in the field by one of the most experienced and insightful leaders. These are my rough notes with a few of the slides. I apologize for any errors and would suggest going to the source for clarity. I offer this here only to show the depth and breadth of material in the field - W.Hay)