Reward, emotion and action Flashcards
How does the brain respond to a rewarding stimulus?
Increasing the release of dopamine NTs
What is the role of the mesolimbic dopamine pathway in reward processing?
Key detector of rewarding stimulus
- > important determinant of motivation and incentive drive
- > activation of this pathway indicates the person to repeat the action leading to that reward
- very old pathway evolutionary wise
Who discovered the mesolimbic reward pathway?
How?
Old and Milner (1954):
- Electrical stimulation in septal area (near NAc)
- Reward (positive reinforcement)
- Seeking behaviour:
- rats self-stimulate repeatedly: pressed the lever repeatedly to receive stimulation
Where are located the most sensitive reward areas?
What makes them the most sensitive?
Along the medial forebrain bundle:
- large connection of fibres between VTA and lateral hypothalamus, towards NAc
- rats would choose receiving stimulation over food or sex
How is dopamine related to rewarding brain stimulations?
- Dopamine neurons are activated during rewarding stimulation
- Injection of DA antagonist causes rats to stop pressing lever (repetitive behaviour)
How do abuse drugs activate the reward pathway?
Opiates, ethanol, nicotine, amphetamine, cocaine…
induce the release of dopamine NTs in NAc and dorsal caudate nucleus (dorsal striatum)
Why are abuse drugs more addictive than natural rewards?
Drug effects on the brain’s reward system minimise those produced by natural rewards:
- Stronger effect on dopamine release: 2 to 10 times the amount of DA than natural rewards
- Effects can last much longer
- Deregulated DA release affects all brain circuits
- > alerting all brain regions of novel rewarding experience
- > recruiting other NT systems
What did PET scans for quantification of dopamine D2/D3 receptor levels in the human brain show on addiction and obesity?
Addicted and obese subjects (vs. controls) had reduced levels of D2 and D3 receptors in striatum
- > new adaptations occur in the brain following over activation of reward pathway
- > brain adjusts to the overwhelming surges in DA and other NTs by producing less DA or reducing number of receptors
What are the consequences for dopamine function in drug abusers?
> DA’s impact on reward circuit becomes abnormally low, and the ability to experience pleasure is reduced
-> abusers eventually feel flat, lifeless, depressed, are unable to enjoy things that they previously enjoyed
> They need to take drugs to try and bring their dopamine function back up
> They develop intolerance, requiring larger amounts of the drug to create the dopamine high
What are the different mechanisms opiates use to increase dopamine release in the nucleus accumbens (NAc)?
VTA neurons are under inhibitory control of local GABAergic interneurons -> prevents DA in NAc
> Mu-opioid receptors are expressed on GABAergic VTA interneurons
- opiates decrease GABA transmission in VTA
- > disinhibition of DA neurons -> DA release in NAc and other terminal areas
> Mu-opioid receptors also expressed on NAc and dorsal striatal neurons
- opiates can also act directly on the NAc, in dopamine-independent manner
What are the different mechanisms alcohol uses to increase dopamine release in the nucleus accumbens (NAc)?
> Alcohol binds to gamma aminobutyric acid A receptors on VTA interneurons
- inhibits GABA transmission in VTA -> disinhibition of dopamine neurons -> DA release
> Alcohol facilitates the release of opioid peptides in VTA
> Alcohol-induced release of opioid peptides directly in NAc can also produce reward in dopamine-independent manner
How does nicotine increase the dopamine release in the nucleus accumbens (NAc)?
Excites dopamine VTA cells directly by binding to nicotinic Ach receptors
-> DA release in NAc
How do psychomotor stimulants (cocaine, amphetamines) increase the dopamine release in the nucleus accumbens (NAc)?
Interact with the dopamine transporter (DAT)
-> increase extracellular DA levels in NAc
What is the current view on rewarding mechanisms?
Dopamine increases motivation components of reward (wanting, seeking)
- it’s not just involved in direct experience of pleasure
What are the regions and circuits involved in the execution of motivated behaviours?
> Ventral striatum receives major cortical input from orbit frontal cortex (OFC) and anterior cingulate cortex (ACC),
and dopaminergic input from VTA and substantia nigra
> Ventral striatum sends projections through VTA and substantia nigra to the ventral pallidum,
> Ventral pallidum projects to PFC via the thalamus (its medial dorsal nucleus)
