Mesolimbic Circuitry Flashcards
How did James Olds study the “pleasure centers” of the brain with mice in the 1950s? What did he find?
Electrode in mouse’s brain- when mouse would press bar, it would receive an electrical impulse
Electrode in “pleasure center”- mouse would press bar at very high rates
What unethical experiments did Heath (psychiatrist) perform to measure the “pleasure centers” of the brain in people? Were his results similar or dissimilar to Olds’?
Stimulated “pleasure centers” of prisoners’ brains with electrodes
Similar
In Olds’ and Heath’s studies, what was the name of the brain path being stimulated?
Medial forebrain bundle
The medial forebrain bundle contains fibers that stretch from which region of the brain to which other region?
Hindbrain to forebrain
What was the result in animals’ bar pressing behavior after their medial forebrain bundles were severed?
Bar pressing went down
Treatment with what neurotoxin had a similar effect to severing the medial forebrain bundle? What was this behavioral effect?
6-hydroxydopamine
Reduction in bar pressing
Mogenson proposed that addiction circuits in the brain connected the ____ system with the parts of the brain that control ____.
Motor
Motivation
Mogenson’s modern day addiction circuitry:
1) Inputs from the ___ system and ____
2) Central part: ___ ___ ___ projects to the ___ ___
3) Outputs to the ___ systems
1) Limbic Cortex 2) Ventral tegmental area Nucleus accumbens 3) Motor
Exposing brain sections to ____ vapors made ____ (neurotransmitter type) fluoresce. How were the neuronal clusters numbered based on their wavelength of fluorescence?
Aldehyde
Monoamines
A or B
The “A” fluorescent pathways were linked to the presence of ____ (neurotransmitter type), whereas the “B” fluorescent pathways were linked to the presence of ____ (neurotransmitter).
Catecholamines
Serotonin
In the fluorescence experiments, what 2 catecholamines were linked to the “A” green/yellow fluorescence?
Dopamine
Norepinephrine
The “A” catecholamine fluorescence pathway was deemed to be a primary component of the ___ ____ ___ (the “pleasure centers” from older experiments).
Medial forebrain bundle
The addiction circuit of today still focuses on the ___ system, the ___ ____ ___, the __ ___, and the ___ ___ ___.
Limbic system
Ventral tegmental area
Nucleus accumbens
Medial prefrontal cortex
Projections and neurotransmitters released:
1) The ventral tegmental area projects to what two other areas and releases what neurotransmitter?
2) The medial prefrontal cortex projects back to what other area and releases what neurotransmitter?
3) The nucleus accumbens projects back to what other area and releases what neurotransmitter?
4) The nucleus accumbens also receive inputs from what other two areas, and what neurotransmitter is released from these inputs?
1) Medial prefrontal cortex, nucleus accumbens Dopamine 2) Nucleus accumbens Glutamate 3) Ventral tegmental area GABA 4) Ventral hippocampus, amygdala Glutamate
The ventral tegmental area is located on the ventral surface of the ____, just medial to the ___ ___. What is the designation for this cell group (think back to the fluorescence groups), and what neurotransmitter is synthesized here?
Midbrain
Substantia nigra
A10
Dopamine
3 forebrain pathways from the ventral tegmental area:
1) ____ (VTA to ___ system)
2) _____ (VTA to ____)
3) _____ (VTA to both ___ and ____ system)
1) Mesolimbic Limbic 2) Mesocortical Cortex 3) Mesocorticolimbic Cortex and limbic
The nucleus accumbens has what 2 subdivisions? How are they similar in terms of input and how are they different in terms of output?
Core
Shell
Both have input from VTA
Different output targets
The nucleus accumbens shell is associated with what region and has functions related to what?
Limbic system
Reward and aversion
The nucleus accumbens core is associated with what region and links what two functions?
Motor systems
Motivation and action
The nucleus accumbens also receives inputs from what 3 other brain regions?
Amygdala
Hippocampus
Thalamus
Dopmaine circuit study:
1) Either norepinephrine or dopamine pathways were damaged with what neurotoxin?
2) Depletion of which neurotransmitter had the greatest effect on cocaine self-administration? What was that effect?
1) 6-hydroxydopamine
2) Dopamine
Decrease in self-administration
Study that sought to cure addiction in humans by damaging dopamine pathway:
1) Was addiction “cured?”
2) What was the side effect?
3) Is damaging the dopamine pathway a viable treatment for addiction?
1) Yes
2) Subjects lost motivation for other activities in addition to drug taking
3) No
All drugs of abuse have pathways that converge on which of 2 possible brain structures?
Ventral tegmental area
Nucleus accumbens
How does the common anatomical pathway of addiction support the DSM IV model of substance abuse?
Diagnosis of substance abuse is substance-independent
What is cocaine’s mechanism of action regarding dopamine?
Binds the binding pocket of the dopamine transporter, preventing dopamine reuptake
What is amphetamine’s mechanism of action regarding dopamine?
Causes a reversal of dopamine transport (rather than taking up dopamine, more dopamine is released)
How are cocaine and amphetamine’s mechanisms of action different from those of opioid drugs?
Opioid drugs bind to a specific receptor, whereas cocaine and amphetamine do not
The main circuit in addiction: ____ projects to ____
Ventral tegmental area
Nucleus accumbens
All drugs of abuse have receptors in or act on what two brain regions? They all increase what neurotransmitter in what area of the brain?
Ventral tegmental area and nucleus accumbens
Dopamine in the VTA
What type of neurons make up over 90% of neurons in the nucleus accumbens? These neurons are (short/long)-projecting ____ (neurotransmitter) (input/output) neurons.
Medium spiny neurons
Long-projecting
GABA
Output
The medium spiny neurons in the nucleus accumbens contain what 2 types of dopamine receptors? Which of these two is part of the direct output pathway, and which is part of the indirect output pathway? Which one is stimulatory, and which one is inhibitory?
D1 and D2
D1: direct, stimulatory
D2: indirect, inhibitory
1) The direct and indirect pathways from the nucleus accumbens both target what area?
2) The indirect pathway passes through what other region before reaching the target area?
1) Ventral tegmental area
2) Ventral pallidum
Normal functions of the addiction circuit:
1) Interface between ___ and ____
2) ___ and ____
3) ___ motivation
4) ____ economy
1) Motivation and action
2) Reward and reinforcement
3) Incentive
4) Behavioral
In incentive motivation, the individual’s internal ____ state interacts with ____ stimuli to drive behavior. Describe an example for this using food and hunger.
Physiological
Environmental
Hunger gives food value and drives the individual’s motivation to obtain the food
Describe the behavioral economy experiment set-up with rodents.
Animal is placed in apparatus with choice to either eat standard food or press bar a certain number of times to obtain a valued food (i.e. sugary cereal)
In the behavioral economy paradigm, what result would indicate that the food obtained through bar pressing is highly valued?
Animal is willing to bar press to receive food rather than eating the standard food on the ground
What is the principle behind microdialysis? What can it be used to measure?
Probes collect molecules of a certain molecular weight (i.e. dopamine) from the brain of a living animal
Can be used to measure chemical changes in the brain related to environmental stimuli
Applying microdialysis to behavioral economy paradigm:
1) What effect does the regular food have on the concentration of dopamine in the rodents’ brains?
2) What effect does the food obtained through bar pressing have on the concentration of dopamine in the rodents’ brains?
3) In general, the more the animal must work for the preferred food, the (less/more) dopamine is released.
1) No increase in dopamine
2) Increase in dopamine
3) More
Behavioral economy: individual is willing to ___ for something they find ____.
Work
Rewarding
In the behavioral economy paradigm, what happens to the rodent’s behavior when the dopamine pathway is damaged? What happens if there is no standard food left out for it?
Rodent eats standard food instead of bar pressing for the preferred food
No standard food- rodent will still bar press
Progressive ratio break point: what is it? A higher break point reveals what about the value of the reward?
Number of times at which an animal will stop pressing a bar continuously for a reward
Higher value
In the behavioral economy paradigm, what happened when the rodents were all given the same food reward upon bar pressing but some were given a drug that increased dopamine? How is this similar to the actions of drugs of abuse?
Rodents that had been given drug to increase dopamine were willing to bar press more times to receive reward
Drugs of abuse artificially increase dopamine, so they drive their users’ motivation to obtain more of them
What is a current field of research regarding addiction circuitry?
Understanding components of circuit that correspond to both normal behavior and drug abuse
