31 - Brainstem Flashcards
Neuromodulatory Systems
Norepinephrine Dopamine Serotonin Acetylcholine Histamine
Slower than GABA and Glutamate systems
Mediated by GPCRs
Noradrenergic System (Norepinephrine)
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.
Dopaminergic System (Dopamine)
2 main centers of production of dopamine:
Substantia Nigra
Ventral Tegmental Area
Massive projections throughout the brain
Serotonergic System (Serotonin)
Raphe Nuclei
(Dorsal Raphe - Projects to forebrain nuclei)
(Median Raphe - Projects to limbmic structures)
(Descending Raphe - Projects to spinal cord)
(Raphe Magnus)
Cholinergic System (Acetylcholine)
Some nuclei in the brainstem
Some nuclei above, in the “base of the brain” (basal nuclei)
Histaminergic System (Histamine)
Main center of production in hypothalamus
Projections to entire CNS
SSRIs
Block presynaptic serotonin transporter
Lengthen the effect of serotonin in the synapse
Tricyclics
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?
LSD
Has a high affinity for the 5-HT 2A receptor
Serotonin receptors
GPCRs Slow onset Affect DNA transcription Long lasting effects Drugs good for chronic disease
Serotinin 1A receptor
Very enriched in the hippocampus
Its action in the hippocampus appears to be responsible for many of the antidepressant effects of SSRIs
Knockout HT1A
You cause anxiety
Knockout HT1B
You cause aggression
Knockout HT2A
You REDUCE anxiety
SSRIs like Fluoxetine
Reaches pharmacological equilibrium quickly, but takes weeks to have therapeutic effect.
Neurotrophic Hypothesis
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
Postreceptor adaptations to SSRIs
Increase cAMP
Increase PKA
Increase CREB (in the nucleus)
Increase BDNF/trkB (a growth factor)
Block BDNF
Reduce the antidepressant effect of SSRIs.
Genetic component of depression
Involves many genes that must each contribute.
Dopaminergic Synapse
Same as Serotonergic, but with dopamine. Still has transporter on presynaptic membrane. Still has MAO.
DOPA
Precursor to Dopamine
L-DOPA
Parkinson’s Med
Postsynaptic Dopaminergic Receptors
D1
D2
D2 Antagonists
Antipsychotic drugs like haloperidol
Arm of the dopaminergic system originating in Substantia Nigra
Loss of Dopamine there leads to parkinson’s
Mesocorticolimbic dopaminergic system
Dopamine produced in the VTA that projects to the cortex and the hippocampus (limbic system)
Important in substance abuse but also in schizophrenia
Sever between forebrain and brainstem
You get sleep EEG patterns
Sever between brainstem and spinal cord
You get normal waking EEG patterns
Orexin System
Narcolepsy