Which structures are involved? Flashcards
Which brain structure is involved?
The mesocorticolimbic dopamine system - dopamine neurons projecting from the VTA to the nucleus accumbens and prefrontal cortex
What is the mesocorticolimbic dopamine system involved in?
Reward and reinforcement
Why do we have a reward system?
We have evolved to have this mechanism which allows us to experience pleasure, so we are more likely to do something
for example, natural reinforcers (food and sex) increase extracellular dopamine in the NA - enables our survival
What do addictive drugs do?
Activate the same system - changed set point hypothesis
Behaviours leading to addiction are repeated
Blockage of DA in their region - reduces reinforcing and reward effects of drugs
They hijack the system - much more powerful than natural reinforces
What is the changed set point hypothesis?
When experiencing pleasure, it is very reinforcing, so we want to do it again - they activate the reward system
What does hijacking the system mean?
Degree of reinforcement so much greater, our system is hijacked because they are so powerful
What is the difference in dopamine release from food vs amphetamine?
Massive release of dopamine when taking amphetamine - 10 times higher - people want this feeling again
What drugs increase dopamine availability in the NA directly?
cocaine/amphetamine - increase availability at synapse by blocking or reversing (pushed out) dopamine transporters
nicotine - direct excitation of VTA neurons by action at nicotinic receptors
What drugs increase dopamine availability in the NA indirectly?
Opiods/cannabinoids - action at opioid or cannabinoid receptors indirectly leads to modulation of VTA activity e.g. inhibition of GABAergic projections onto VTA neurons allows them to fire resulting in increases in DTA
How is associative learning relevant?
Sensory information: people, places, emotions present at the same when taking the drug and when DA release occurs is associated with reward - memory
things irrelevant before are now important
What will coincident firing of DA in NA induce?
LTP and strengthen synaptic connections
sensory inputs from brain
dopaminergic inputs from VTA
reward associated cues will trigger reward seeking behaviour and cause problems associated with relapse
What does the environment serve as?
A trigger to reexperience memories - increase of dendritic spines, forming new synapses
What does dopamine enhance and how?
LTP
dopamine at D1 receptor (Gs coupled) so stimulate AC
cAMP and PKA produced
modifies glutamate transmission allowing LTP
CREB
mediates gene transcription and new protein synthesis
somatic re-modelling - increased spines
long term molecular and cellular changes, memories in pathways trigger relapse
Why does relapse occur?
Because of LTP - strengthens learning and can trigger craving, years later
What happens to the frontal system?
It is dysfunctional in substance abuse - reduced glucose metabolism
Hypoactivity in these brains - can cause loss of control and compulsive drug taking, loss of inhibitory control and inability to restrain
