Drugs that Impact the Glutamatergic System - PCP and Ketamine

Animals will __________ PCP: they will press a lever to have PCP infused into the brain, showing that PCP is _________

self-administer, reinforcing

Ketamine was a molecule that worked like PCP but had _______ affecting the body, _____ potent, less __________ side effects (still dissociative), and safe for ________ to be used as an anaesthetic

shorter time, potent, behavioral, children

What type of NT are PCP and Ketamine?

Non-competitive antagonists at NMDA receptors

Once NMDA receptors are open, PCP and Ketamine can enter through a _____ and ______ it

pore, block

What happens when PCP/Ketamine get into channels and block channel flow?

Drugs get trapped inside the pore and the channel inactivates

What type of neurons are GABAergic interneurons?

Inhibitory

When PCP/Ketamine block channel flow in NDMA receptors in GABAergic (inhibitory) interneurons, what happens?

Less GABA release and inhibition on post-synaptic cell

If GABAergic (inhibitory) interneurons do not release GABA to inhibit the postsynaptic cell, what happens to the postsynaptic glutamatergic neuron?

More glutamate release and enhance AMPA receptors

Ultimately, PCP/Ketamine blocking NMDA channels causes ______ inhibition in the presynaptic GABAergic interneuron so _________ excitation of the postsynaptic glutamatergic neuron

decreased, increased

Increased Glutamate symptoms of PCP/Ketamine mirrors Schizophrenia Psychotic symptoms (dissociation and hallucinations)

Glutamate Hypothesis of Schizophrenia

What are the two downstream effects of PCP and Ketamine?

1. Increased Dopamine release causes more PCP/Ketamine use

2. Antidepressant

If Ketamine gets into the VTA in the brain, it _________ firing which leads to more ________ going to different areas of the brain, causing ________.

increases, dopamine, addiction

Ketamine is thought to _________ BDNF (prevents cell death from depression chronic stress) by increasing ________ receptor activity, ultimately resulting in ____________ effects

increase, AMPA, anti-depressant