Brain Mechanisms of Self-Regulation Failure and Stress Flashcards
Neuropharmacology
- Dopamine is made in the cell body
- Dopamine is shipped down the axon
- Dopamine is releases from the terminal
- big part of how amphetamine work and will kill presynaptic terminal - Dopamine stimulates dopamine receptors
- hypo-dopamine system- less than average dopamine
- most abused substances manipulate the dopamine system
DAT- dopamine transporter
- major target for cocaine
- blocks the re-uptake up dopamine which allows you the stay high longer
- extends the synaptic lifespan of dopamine
Physiology of neurotransmission – synaptic transmission
- Action potential
- Transmitter release
- Receptor activation
- Neurotransmitter inactivation
Sites of rewarding drug action
- dopamine, opioid peptide neuron and synapses
a. Neurotransmitter release
b. Neurotransmitter re-uptake
c. Receptor agonist or antagonist action
opioid peptides
-endorphines
dinorphines- pro-pain or depression
Neurobiology of Dependence
- Addiction is a reward deficit disorder
- person who has a susceptibly and can not achieve the same amount of dopamine reward as the average person - Addiction is a stress surfeit disorder
- has and excess of stress or anxiety
- drive us to cravings - Addiction is a self-regulation disorder
- impairments in areas in the brain that helps us make desicions
Neurocircuitry of Addiction/Neurochemistry of Reward- Binge/Intoxication
. Mesolimbic dopamine system
- Ventral tegmental area(VTA)
- central component of how we feel reward and dopamine in the brain
- ascending projections to the front of the brain
- have selective type of inputs the certain areas of the brain
-Go to-
-hypothalamus-
critical structure for feeding, sex, ect
-amygdala- involved in stress and anxiety
-and the Nucleus accumbens
- Nucleus accumbens
- major highway for the euphoric feeling of reward
-finally goes to prefrontal cortex ad allow us to make decisions about reward
Neurocircuitry of Addiction- Withdrawal/ Negative Affect Stage
Amygdala
-still links to nucleus accumbens to drive negative reinforcement
Neurocircuitry of Addiction- Preoccupation/ Anticipation
- subareas of the prefrontal cortex
- projection to the central nucleus of the amygdala
- adding something more to the system
- with the complexity also comes risk
- prefrontal cortex- decision making, working memory, planning
- planning is the main problem for transcendence - orbitofrontal cortex- separates compulsive use from impulsive use
- Hippocampus- cues like being in the environment that reminds you of your addiction
Where does euphoria happen in the brain?
Dopamine release from the VTA in the the nucleus accumbens
Prefrontal cortex
major area where decisions about reward are made
Cocaine self-administration
mice develop the same habits as humans and start to make a pattern in administration time based on the dosage
-learn to like it and how much or little they like
The Nucleus Accumbens
- Receives dopaminergic input from VTA
- Major site of action for many drugs of abuse
- Key point of convergence in reward circuitry
- Grand Central Station for rewards
Brain Regions by reinforcement and stage of addiction cycle
- Positive – binge/intoxication- nucleus accumbens
- Negative – withdrawal/negative affect-amygdala
- Conditioned – preoccupation/anticipation-frontal cortex and basolateral amygdala
Mood Changes Associated with Plasma Levels of Cocaine during Coca Paste Smoking
- High highs and low lows
- also applies to non addictive drugs like gambling and binging on food
Stress-definitions
- Nonspecific response to any common demand upon the body (Hans Selye)-anything that challenges to body
- Alteration in psychological homeostatic processes (Susan Burchfield)-somthing that challenges or changes us psychologically
-most time when we binge in any form it is to relieve stress
Corticotropin releasing factor (CRF) in the Hypothalamus
a. Activation of endocrine (hormonal) stress response
b. Stimulates release of ACTH from pituitary
c. ACTH in turn stimulates release of glucocorticoids from adrenal gland
d. Glucorticoids increase blood sugar, suppress immune function and breakdown fats
Corticotropin releasing factor (CRF) in the Medulla
a. Activation of sympathetic nervous system-release of norepinephrine (noradrenaline)
b. Stimulates nerve leading to adrenal medulla- release of epinephrine (adrenaline)
c. Norepinephrine and epinephrine increase heart rate, increase blood pressure and produce bronchial dilation
Corticotropin releasing factor (CRF) in the Amygdala
a. Coordination of behavioral responses to stress
b. May be important in aspects of self-regulation failure associated with addiction
vivo Microdialysis
- Allows sampling of neurochemicals in conscious animals (correlate brain chemistry with behavior).
- Implanted so that semi-permeable probe tip is in specific brain region of interest.
- Substances below the membrane MW cutoff diffuse across membrane based on concentration gradient.
- Both neurochemical sampling and localized drug delivery are possible.
Executive Function
Conceptualized as the ability to organize thoughts and activities, prioritize tasks, manage time and make decisions.
Neurobiological substrates include lateral prefrontal cortex and orbitofrontal cortex .
Deficits in the function of lateral prefrontal cortex and orbitofrontal cortex produced by drugs of abuse can lead to disinhibition and poor choices
Hypofrontality
Dorsolateral Prefrontal Cortex
- working memory, planning, strategy
- Deficits: impairments in planning, strategy, working memory
Anterior Cingulate Cortex
facilitates on line maintenance and selection of responses particularly under high attentional demands, planning, self-initiation and self-monitoring of goal-directed behaviors.
-Deficits; problems of initiation (mutism), compulsive checking like OCD
Ventrolateral Prefrontal Cortex
Response inhibition, sustained attention, memory retrieval, rule generation and shifting
-Deficits: problems in cognitive flexibility, memory and response inhibition
Orbitofrontal Cortex (including ventromedial PFC)
assignment of value, integration of reward and punishment
-Deficits: reinforcer devaluation, reversal learning (cognitive inflexibility), delay discounting (‘myopia for the future’), decision making quality
Hippocampus
consolidation and encoding of memory
Deficits: problems of spatial, verbal recall, episodic and contextual/configural memory
From Moderation to Spiraling Distress
A. Within system neurochemical changes 1. Dopamine goes down 2. Opioid peptides goes down B. Between system neurochemical changes 1. CRF goes up
Stages of the Addiction Cycle
Know whats up and whats down
