Lecture 7: Neurophysiology of Reward and Addiction Flashcards
What is motivation?
A process that mediates goal-directed responses or goal-seeking behavior to changes in the external or internal environment
What is saliency?
Something important in the surrounding env. worth paying attention to
What is a reward?
Objects, stimuli, or activities that have positive value
What is aversion?
A negative reinforcement of behavior that the individual will learn to avoid future encounters
What is pleasure?
A positive sensation
What is the purpose of pleasure?
Promote behaviors that are consistent with survival of self and the species
What NT plays a role in pleasure reward seeking behavior?
Dopamine
How do drugs affect dopamine concentration?
Will increase extracellular concentration of dopamine in limbic areas and prevent reuptake of dopamine
What is a salience stimuli?
A noticeable stimuli that can be arousing or elicits a behavioral switch
Why are addicts at a great risk for relapse when they visit places they had taken drugs at?
The stimuli around them are salient (noticeable)
The stimuli itself can increase dopamine and elicit desire for drugs.
Briefly, how does the mesolimbic system work?
Dopamine is produced in VTA
VTA dopaminergic fibers are projected to nucleus accumbens.
What is the main function of the nucleus accumbens?
Suppress sensations of pleasure and reward
What structures constitutively activate (via EAA like glutamate) nucleus accumbens?
Hippocampus
Amygdala
Prefrontal cortex (PFC)
What type of neurons does the nucleus accumbens release?
GABA (inhibitory)
What pathway occurs when you do something that elicits a reward?
- Dopamine neurons synthesized in VTA project to nucleus accumbens.
- Dopamine released into NA, inhibits it.
- NA activity decreases, resulting in a sensation of pleasure
What stimulates the VTA when you engage in behavior or activity that results in rewards?
Pre-frontal cortex: EAA
Tegmental nuclei: ACh
Hypothalamus: Orexin (from food)
What suppresses the VTA?
- Nucleus Accumbens: GABA
2. Nucleus Accumbens: Dynorphin (transmitter)
What is the dopamine-hypothesis reward?
Inactivation of nucleus accumbens via dopamine from VTA
What activities can increase endogenous opioid signaling?
Exercise
Ethanol
Other stuff
What receptors do opioid signaling utilize to activate dopaminergic receptors at VTA?
Mu receptors
How does opioid signaling work?
- Inhibit local VTA interneurons that normally suppress dopaminergic neurons in VTA
- Disinhibit dopaminergic neurons
- Activate nucleus accumbens local interneurons to inhibit the release of GABA
- Activate pre-frontal cortex
What is the result of endogenous opioid signaling?
Pleasure
Euphoria
From a neurobiological perspective, what does addiction probably result from?
Recurrent supraphysiologic perturbations in dopamine system
Chronic drug exposure alters the morphology of neurons in dopamine-regulated circuits
How can drugs change things at a cellular level?
Alter expression of certain transcription factors and proteins involved in neurotransmission in brain regions regulated by dopamine
How can drugs change things at a neurotransmitter level?
Abnormal NT levels for dopamine, glutamate, GABA, opioids, serotonin
Where are lasting memories of the good feelings associated with drugs created?
Memories made in hippocampus
What structure mediates craving?
Amygdala
When the abuser seeks out drugs, what structure is involved in the poor decision making?
Orbitofrontal cortex
How does the activation of calcium-calmodulin-CREB mechanism work?
Promotes production of dynorphin in nucleus accumbens to shut off VTA and dopaminergic signaling
What is physical dependency?
Chronic use of a tolerance-forming drug, in which abrupt or gradual drug withdrawal causes unpleasant physical symptoms
Why does physical dependency occur?
Excessive noradrenergic output from the locus ceruleus (involved in arousal and vigilance)
CREB dependent up-regulation of target genes in locus ceruleus.
When are the FosB and AP-1 genes up-regulated?
Stress
Drugs of Abuse
How do natural reinforcers (food, sex, exercise) differ from drugs?
Natural Reinforcers: Firing of neurons stop when event concludes
Drugs: Dopamine release continues after activity
How does dopamine change the reward circuitry?
Dopamine can alter a fearful stimuli to a pleasurable one
Ex: Before hearing a bell could be scary, but now hearing a bell is associated with euphoria from drugs
How do addicted brains differ from non-addicted brains?
Conditioned cues reinforce saliency of substances, increasing behavior to find and consume drugs.
These cues override prefrontal cortex’s control of behavior
What role does the substantia nigra and dorsal striatum play in pleasure/reward-seeking behavior?
Control motor response associated with navigating the environment for desirable activity
What are differences between conditioned responses and drug-associated cues?
Conditioned responses: cues to drug-taking in specific social circumstances
Drug-associated cues: powerful cues that can elicit drug urges and physiologic responses w/o taking drug
What role does the locus ceruleus play?
Involved with physiological responses to stress and panic
Synthesis of norepinephrine
What does CREB mediate in the locus ceruleus?
Physical dependency due to excessive noradrenergic output from locus ceruleus
