Antipsychotics (PD Week 6) Flashcards
What is schizophrenia
a psychotic disorder characterized by loss of contact with the environment by noticeable deterioration in the level of functioning everyday life
What are some positive symptoms of schizophrenia
- delusions
- hallucinations
- disorganised speech
- disorganised behaviour
What are some negative symptoms of schizophrenia
- social withdrawal
- flat emotional response
- anhedonia (inability to feel pleasure)
- lack of motivation
Describe the 3 dopaminergic pathways
- A9 pathways - substantia nigra > caudate putamen
- A10 - VTA > nucleus accumbens (mesolimbic pathway)
- A10 - VTA > cerebral cortex (mesocortical pathway)
What pathway is damaged in schizophrenia
A10 pathway (mesocortical pathway) - there is a loss of dopamine to the prefrontal cortex which leads to reduced inhibitory feedback - elevated levels of dopamine are released to the limbic site
Where do antipsychotics target
they block dopamine receptors in the limbic regions
What is the main difference between atypical and typical antipsychotics
atypical antipsychotics have fewer side effects than typical antipsychotics
How do atypical antipsychotics work
they work as dopamine antagonists
they have low affinity for D2 receptors
they have antagonist activity at 5-HT2a receptors
they have little effect on motor function due to avoiding the A9 pathway
to get optimal effect as an antipsychotic they are mixed 5HT2a/DA and D2 receptor antagonists
What is sensory motor gating in terms of antipyschotics
the ability of a sensory event to suppress a motor response, can be measured operationally via prepulse inhibition (PPI) of the startle response. Prepulse inhibition is normally defective in schizophrenia as they are unable to filter out unnecessary input and irrelevant information
How can prepulse inhibition be induced (for schizophrenics)
- drugs
- neurochemical lesion
- behavioural/neurodevelopment manipulation
How is glutamate involved in schizophrenia positive symptoms of the mesolimbic pathway
Mesolimbic (A9 pathway) is normally controlled by glutamate input
NMDA hypofunction is associated with schizophrenia positive symptoms
hypofunction of NMDA = decrease in glutamatergic input on GABA interneurons which leads to decreased stimulation of GABA interneurons
= overactivity of mesolimbic pathway
How is glutamate involved in schizophrenia negative symptoms of the mesocortical pathway
activity of dopaminergic pathway is directly due to glutamatergic neuron - no GABA
decrease in glutamatergic neuron due to hypofunction of NMDA receptor = decrease in dopamine to prefrontal cortex = negative symptoms
