Midbrain Modulation of
Motivation
Nice place Sydney, but the
weather is much the same as Boston.
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Extent of Drug Abuse Problem – USA #1
Intravenous Drug
Self-Administration Setup
Electrometer and ==>
Drug Infusion Pump ==>
Isolation Chamber ==>
Operant Chamber ==>
Subject
==>
electrode implanted
and jugular catheterised
Intravenous Drug
Self-Administration
(IVSA)
FR-2 drug reinforcement:
(0.25 mg/kg i.v. injection of amphetamine)
Conditioned stimulus:
(5-sec light flash and 30-sec light “off” period) paired with each injection
(drug self- and yoked-groups) or saline (vehicle yoked-group)
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Changes in Accumbens
Dopamine on:
IVSA TEST DAY 7 CONDITIONED TEST DAY 9
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Post-Amphetamine Binge
Abstinence Period
Abstinence and Amphetamine
Challenge
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Dopamine Model of Drug
Self-Administration
1. Binge 2. Crash 3. Burn (Relapse)
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Basic Requirements For
Studies:
1. Well-equipped lab
2. Enthusiastic students
3. Reasonably lucid supervisor
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A few reasons why
I came back to the US.
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Analysis of Afferent
Circuitry Modulating
Dopamine Cell Burst Firing and Release
Prefrontal Cortex
Subthalamic Nucleus
Pedunculopontine Nucleus
Superior Colliculus
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A New Enlightening Means of
Modulation
Superior Colliculus to Substantia Nigra
My Enlightened Colleague
Prof. Peter Redgrave
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Light-Evoked Dopamine
Release in Striatum
Electrochemical Recording
and Drug Infusion Setup
Light-Evoked Dopamine
Release in Striatum:
GABA-A-r Antagonism in SC Required
Light-Evoked Dopamine
Release in Striatum:
Potentiation by Dopamine Re-uptake Blockade
Light-Evoked Dopamine
Release (ECHEM)
versus
Light-Evoked Dopamine Cell Activity (EPHYS)
A New Enlightening Means of
Modulation
Visually-Evoked Dopamine Transmission
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DBS Collaborators
Emad Eskandar, Ramin Amirnovin, Dennis Meredith, and Kendall Lee
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Synaptic Plasticity: Long-Term Depression
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Long-Term Potentiation and
Dopamine Terminal Release:
The Next Step
Receptor Model of Cortical
and Mesopontine Modulation of Midbrain Dopamine Cell Activity and Forebrain
Transmission