33 Neuropharmacology Intro

Question 1

How does chronic psychosocial stress sequelae compare with the symptoms of clinical depression?

Answer 1

they are very similar if not the same, one proceeding from the other; there also exists a correlation between what is observed during learned helplessness and depression

Question 2

What does the monoamine hypothesis of depression state?

Answer 2

the under-activity of monoamine pathways contributes to depression symptoms (this is consistent with the sequelae of chronic stress)

Question 3

Where do monoamine pathways originate and project to?

Answer 3

monoamine pathways all originate in clusters of neurons in the midbrain and pons, and these discrete nuclei send widespread projection throughout the forebrain (where receptors for monoamines are found) including the basal ganglia, cortex, hippocampus and amaygdala

Question 4

Name three neurotransmitter systems that are dysregulated in depression and what is their respective functions?

Answer 4

norepinephrine (arousal and attention), serotonin (mood, sleep and affect) and dopamine (movement and motivation)

Question 5

What are the nuclei that release NE, 5HT and DA respectively.

Answer 5

locus coeruleus, raphe nuclei and mesolibocortical/ mesostiatal

Question 6

Drugs that treat depression increase neurotransmission at which synapses (named for their neurotransmitter)

Answer 6

NE, 5HT and DA

Question 7

Name the precursor molecule for NE, 5HT and DA and then the molecule that is responsible for enzymatic break down of monoamines

Answer 7

tyrosine (norepi and dopamine) and tryptophan (serotonin); monoamine oxidase (MAO)

Question 8

What were the actions and side-affects of MAO inhibitors/ tricyclics?

Answer 8

their action was to inhibit the action of monoamine oxidase so neurotransmitters were readily recycled; side affects were brought on by any amino acids that were converted to monoamines, compounding the surplus of monoamines (leading to cardiac symptomsL pounding/fast heartbeat, sweating, tremors dizziness, increased BP)

Question 9

What was the benefit of second generation antidepressants?

Answer 9

they were more selective, to specifically serotonin or norepi, these drugs inhibit the reuptake of monoamines so they are present in the cleft longer

Question 10

What are the disadvantages of SSRI and SNRIs

Answer 10

their effects require substantial time to take affect (therapeutic lag is attributed to re-development of plasticity in target neurons) and symptoms can return if medication is discontinued

Question 11

What are the aims of 3rd generation antidepressants?

Answer 11

goal: develop fast-acting drugs that enhance synaptogenesis- target the mechanisms of plasticity itself instead of indirectly through monoamines

Question 12

How do antidepressants affect the dendritic atrophy that seen as a result of chronic stress?

Answer 12

antidepressants may reverse dendritic impoverishment via growth factors

Question 13

What are the positive, negative and cognitive symptoms of schizophrenia?

Answer 13

positive: psychosis (hallucinations, paranoia, delusions, perpetual abnormalities); negative: emotional blunting, anhedonia, and social withdrawal; cognitive: thought disorder (disorganization, perseveration, cannot formulate/sustain plans)

Question 14

How was the dopamine hypothesis of schizophrenia developed?

Answer 14

psychostimulants were observed to potently increase DA release and cause psychosis (hallucinations, paranoia and delusions) by “hijacking” monoamine reuptake proteins and spilling monoamines back into synapse

Question 15

Describe/name the two distinct dopaminergic systems.

Answer 15

mesocorticolimbic (schizophrenia related) and nigrostriatal (moto-related)

Question 16

Excessive _____ in the nucleus accumbens may contribute to schizophrenia.

Answer 16

dopamine

Question 17

What was the action of 1st generation antipsycotics (neuroleptics) and what were their adverse affects?

Answer 17

neuroleptics potently antagonize DA receptors, their down fall was that they only adequately addressed positive symptoms while showing now improvement in negative or cognitive symptoms as well as causing Parkinsonian like syndromes, also treatment resistance was also a problem

Question 18

Atypical antipsycotics (2nd generation) where able to treat which symptoms.

Answer 18

they controlled positive and negative symptoms as well as those patients show were neuroleptic resistant (clozapine= prototype)

Question 19

What are the drawbacks of atypical antipsycotics?

Answer 19

they can produce lethal agranulocytosis, and metabolic side affects (hyperlipidemia, insulin-resistance and weight gain) and cognitive symptoms are largely unchanged

Question 20

What is the cellular basis for schizophrenia?

Answer 20

there is neuronal disorganization of pyramidal cells with no volume loss which is thought to be a neurodevelopmental disfunction (over pruning in the prefrontal cortex but lack neuronal pruning in subcortical structures

Question 21

Generally, currently used antipsycotics improve schizophrenia by blocking_____ and ____

Answer 21

D2 and 5HT2 receptors (this is to counter excessive ventral striatum monoamine levels (focus on subcortical limbic brain structures) and imbalance of fronto-striatal signaling