31 - Brainstem

Question 1

Neuromodulatory Systems

Answer 1

Norepinephrine
Dopamine
Serotonin
Acetylcholine
Histamine

Slower than GABA and Glutamate systems
Mediated by GPCRs

Question 2

Noradrenergic System (Norepinephrine)

Answer 2

Nuclei located in the brainstem
Neurons project to whole CNS
(Upward to forebrain and limbic systems, and downward to spinal cord)
Norepi is synthesized in localized part of the brain, but can be released anywhere.

Question 3

Dopaminergic System (Dopamine)

Answer 3

2 main centers of production of dopamine:
Substantia Nigra
Ventral Tegmental Area
Massive projections throughout the brain

Question 4

Serotonergic System (Serotonin)

Answer 4

Raphe Nuclei
(Dorsal Raphe - Projects to forebrain nuclei)
(Median Raphe - Projects to limbmic structures)
(Descending Raphe - Projects to spinal cord)
(Raphe Magnus)

Question 5

Cholinergic System (Acetylcholine)

Answer 5

Some nuclei in the brainstem

Some nuclei above, in the “base of the brain” (basal nuclei)

Question 6

Histaminergic System (Histamine)

Answer 6

Main center of production in hypothalamus

Projections to entire CNS

Question 7

SSRIs

Answer 7

Block presynaptic serotonin transporter

Lengthen the effect of serotonin in the synapse

Question 8

Tricyclics

Answer 8

Mono Aminoxidase Inhibitors (MAO Inhibitors)
Prevents the intracellular degradation of serotonin, like an anticholinesterase, but inside the bouton. Perhaps it increases serotonin in the synaptic cleft through concentration gradients preventing as much reuptake?

Question 9

LSD

Answer 9

Has a high affinity for the 5-HT 2A receptor

Question 10

Serotonin receptors

Answer 10

GPCRs
Slow onset
Affect DNA transcription
Long lasting effects
Drugs good for chronic disease

Question 11

Serotinin 1A receptor

Answer 11

Very enriched in the hippocampus

Its action in the hippocampus appears to be responsible for many of the antidepressant effects of SSRIs

Question 12

Knockout HT1A

Answer 12

You cause anxiety

Question 13

Knockout HT1B

Answer 13

You cause aggression

Question 14

Knockout HT2A

Answer 14

You REDUCE anxiety

Question 15

SSRIs like Fluoxetine

Answer 15

Reaches pharmacological equilibrium quickly, but takes weeks to have therapeutic effect.

Question 16

Neurotrophic Hypothesis

Answer 16

Downstream of the increase in serotonin, there are growth-related changes that are responsible for the antidepressant effect.

Candidates:
Halt hippocampal atrophy
Prevent stress-induced dendritic shrinkage
Increase hippocampal neurogenesis

Question 17

Postreceptor adaptations to SSRIs

Answer 17

Increase cAMP
Increase PKA
Increase CREB (in the nucleus)
Increase BDNF/trkB (a growth factor)

Question 18

Block BDNF

Answer 18

Reduce the antidepressant effect of SSRIs.

Question 19

Genetic component of depression

Answer 19

Involves many genes that must each contribute.

Question 20

Dopaminergic Synapse

Answer 20

Same as Serotonergic, but with dopamine. Still has transporter on presynaptic membrane. Still has MAO.

Question 21

DOPA

Answer 21

Precursor to Dopamine

Question 22

L-DOPA

Answer 22

Parkinson’s Med

Question 23

Postsynaptic Dopaminergic Receptors

Answer 23

D1

D2

Question 24

D2 Antagonists

Answer 24

Antipsychotic drugs like haloperidol

Question 25

Arm of the dopaminergic system originating in Substantia Nigra

Answer 25

Loss of Dopamine there leads to parkinson’s

Question 26

Mesocorticolimbic dopaminergic system

Answer 26

Dopamine produced in the VTA that projects to the cortex and the hippocampus (limbic system)

Important in substance abuse but also in schizophrenia

Question 27

Sever between forebrain and brainstem

Answer 27

You get sleep EEG patterns

Question 28

Sever between brainstem and spinal cord

Answer 28

You get normal waking EEG patterns

Question 29

Orexin System

Answer 29

Narcolepsy