Cocaine and Morphine Induced Silent Synapses

These flashcards cover key concepts and findings from the lecture on the mechanisms of morphine and cocaine in generating silent synapses.

What is the main question of the study regarding cocaine and morphine?

How do cocaine and morphine induce opposing synaptic modifications in the nucleus accumbens despite similar behavioral outcomes?

What are silent synapses?

Silent glutamatergic synapses contain functional NMDARs and absent or unstable AMPARs.

How does cocaine exposure generate silent synapses in the NAcSh?

Cocaine exposure generates silent synapses by inserting new NMDARs into the synaptic cleft.

What mechanism does morphine use to generate silent synapses?

Morphine exposure generates silent synapses through the internalization of AMPARs from pre-existing synapses.

What is the function of the Tat-GluA2 peptide?

Tat-GluA2 blocks the endocytosis of AMPARs.

What are the results of the minimal stimulation assay after drug exposure?

It measures the excitatory postsynaptic currents (EPSCs) in morphine, cocaine, and saline-exposed mice.

What did the study find regarding the percentage of silent synapses after morphine exposure?

The silent synapse percentage for morphine exposure increases gradually over the exposure period then decreases dramatically after withdrawal.

How did cocaine and morphine affect spine dynamics according to the study?

Cocaine increased total spine density and protrusions, while morphine reshaped spines without changing total density.

What did the findings suggest about the D1R and D2R MSNs after withdrawal?

After withdrawal, excitatory drive is biased towards D1R MSNs for both drugs, showing a circuit-level rebalancing.

How did GluA23Y peptide affect morphine-induced behaviors?

The co-administration of GluA23Y selectively impaired the retention of morphine-induced conditioned place preference (CPP).

What is the role of parvalbumin (PV) interneurons as discussed in the limitations?

It questions whether PV interneurons in the NaC are influenced by drug conditioning.

What major questions remain unanswered at the end of the discussion?

Is silent synapse generation cell type and projection specific? Is there a distinct role for D1R and D2R MSNs after chronic drug exposure?

Which two follow-up studies are referenced at the end of the notes?

Wright et al. (2019) discusses cocaine memory, and Zinsmaier et al. (2021) focuses on cocaine-induced adaptations in the nucleus accumbens.