Neurophysiology of Reward and Addiction Flashcards
What is saliency?
Something important in the surrounding environment worth paying attention to
What is hedonia?
Stimuli or environmental changes that are arousing or elicit an attentional-behavioral switch
In what areas do drugs of abuse increase extracellular dopamine concentrations?
Limbic regions, including the NA
How do drugs such as cocaine, amphetamine, methamphetamine, and ecstasy increase dopamine?
By directly inhibiting dopamine reuptake or promoting dopamine release
How do drugs such as nicotine, alcohol, opiates, and marijuana increase dopamine?
Indirectly via other neuron receptors that modulate dopamine levels
What makes up the mesolimbic system?
Nucleus accumbens, ventral tegmental area, limbic system, and prefrontal cortex
What is the main function of the NA?
Suppress sensations of pleasure/reward
How does the NA work?
It is constitutively activated by a constant trickle of EAAs from the hippocampus, amygdala, or PFC. It releases GABA at the PFC to keep the brain in a reward-neutral state
How does the reward circuit work?
VTA neurons project to NA and release dopamine which inhibits NA neurons. Inhibition of NA (inhibitory GABAergic) neurons results in sensation of pleasure
How is the VTA activated during reward?
By EAAs (PFC), orexin (hypothalamus), or ACh (tegmental nuclei)
What is the reward feedback circuit?
Projections of GABAergic neurons from the NA back to the VTA. Dynorphin (an opioid) released as a cotransmitter that binds to kappa-opioid receptors in VTA. Together suppress additional release of DA from VTA to halt reward process
What is the dopamine-independent reward pathway?
Utilizes endogenous opioids
How do opioids work in the reward network?
Activate dopaminergic neurons via mu receptors in VTA
Activate local interneurons in NA which inhibit GABAergic neurons
Activate PFC directly
What region of the brain is involved in compulsive behavior?
Orbitofrontal cortex
Which region of the brain regulates disinhibition
Cingulate gyrus
What are conditioned associations?
Memories that associate good feelings with the circumstance and environment in which they occur
What is CREB?
cAMP response-element binding protein, is shorter acting (days)
What is physical dependency due to?
Excessive noradrenergic output from locus ceruleus and CREB-dependent upregulation of target genes in locus ceruleus
What is long-term potentiation?
Persistent increase in synaptic strength following high-frequency stimulation of chemical synapse. Increased phosphorylation of AMPA receptors and insertion of AMPA receptors in post-synaptic membrane (short term). Also activation of calcium-calmodulin-CREB (long term).
What is a prominent target for CREB?
Dynorphin- Which is working with GABA in the feedback circuit to halt Dopamine release
When would you see an increase in FosB (or AP-1)?
with increased stress or abusing drugs
