07 | Addiction Flashcards
(69 cards)
The reward pathway is also known as ___. It is made up of…
- cortical limbic system pathway
2. VTA-NAc-FC
Major sources of DA in the brain
- VTA (reward)
2. SN (voluntary movement)
Effect of opioids on DA
inhibit GABA ⇒ ↓ inhibition of DA release ⇒ more DA
Effect of nicotine on DA
↑ dopaminergic innervation
Effect of cocaine, amphetamines on DA
↑ DA release, ↓ DAT ⇒ more dopaminergic innervation
Neuron composition of VTA
60% DA
40% GABA
DA on NAc has what effect?
reward & reinforcement
DA on PFC has what effect?
exclusive function (loss of control)
DA on hippocampus has what effect?
memory
DA on amygdala has what effect?
emotions
What 2 things are needed for withdrawal response?
- Stress
2. DA
What was the experimental procedure that determined the relationship between stress and reward pathways? What was the result?
double labelling + in situ hybridization
In drug users, neuroadaptation of VTA DA neurons lead them to express CRF
What happens to synaptic plasticity in drug addiction?
- Promote LTP of dopamine (reward) pathways
- Promote LTD of GABA (inhibitory) pathways
- Loss of synaptic plasticity in NAc → linked to inability to control drug intake
How does cocaine promote LTP in certain pathways? What is 1 short-term response?
↑ AMPA on VTA DA neurons⇒ stronger EPSP (LTP)
↑ dendritic spine density in VTA DA neurons ⇒ ↑ possibility of forming synapses (this is only for short-term response)
Cocaine-induced LTP can be blocked by…
MK-801 (NMDA blocker)
Which subunits of AMPA-R are not likely involved in LTP response to cocaine?
GluA1 and GluA2
What eventually stops the ↑ AMPA LTP response?
mGluR1 (Ro 67)
What is Ro 67?
mGluR1 activator
LTP response is _synaptic, while LTD is _synaptic
- pre
2. post
2 ways to induce LTD at VTA GABA-DA synapses
- LFS
2. Morphine
Mechanism used by LFS to cause LTD
decrease number and conductance of GABA(A)-R
Does LTD depend on NMDA-Rs?
No
Actions of morphine to cause LTD
- Prevent LFS-LTD
2. induces its own LTD (unclear)
Drugs that can induce LTD
nicotine, morphine, cocaine, alcohol