Drugs Brain and Mind - Chapter 6: Serotonin

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16 Terms

1

serotonin (5-hydroxytryptamine, 5-HT)

monoamine, indoleamine

cannot cross BBB, neurons must synthesize it

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2

dietary tryptophan and 5-HT synthesis

tryptophan competes with large neutral a.a. for transport across BBB

ratio between amount of tryptophan and a.a determines whether 5-HT synthesis is stimulated in the brain

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3

serotonin autoreceptors

terminal: 1B and 1D

somatodendritic: 1A in raphe nuclei

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4

para-chloroamphetamine (PCA)

indirect 5-HT agonist

depletion of brain serotonin and neurotoxicity

not in clinical use

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5

fenfluramine

indirect 5-HT agonist

reverses SERT and disrupts vesicular storage

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6

4-methylenedioxymethamphetamine (MDMA)

indirect 5-HT agonist (ecstasy, molly)

high affinity ligand for SERT, stimulates 5-HT efflux from synaptic terminals via a reverse-transport mechanism and blocking of VMAT2

SSRIs block MDMA’s ability to bind SERT and stimulate 5-HT release

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7

serotonin syndrome in humans

severe toxicity associated with combinations of agents that act through different mechanisms

clinical triad of abnormalities:

  1. cognitive effects

  2. autonomic effects

  3. somatic effects

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8

dorsal and median raphe nuclei

almost all 5-HT cell bodies in the CNS found along midline of the brainstem

nearly all forebrain regions receive 5-HT innervation

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9

5-HT1A (Gi)

in the forebrain, mostly hippocampus: postsynaptic receptors

in the raphe nuclei (brainstem): somatodendritic autoreceptors

reduce cAMP by inhibiting adenylyl cyclase

increase opening of K+ channels » hyperpolarization

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10

5-HT2A receptors (Gq)

highly expressed in cortex, striatum, and NA

activate the phosphinositide second-messenger system (PLC)

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11

lysergic acid diethylamide (LSD) and psilocybin

hallucinogenic effects

stimulation of 5-HT2A receptors

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12

5-HT2A receptor antagonists

clozapine and risperidone

antagonize 5-HT2A receptors and D1 and D2 receptors

more pronounced 5HT antagonisms than DA

fewer movement-related side effects than D2 receptors

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13

5-HT and aggression

brain areas involved in aggression receive substantial serotonergic innervation and express several 5-HT receptor subtypes

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14

5-HT and Anxiety

SSRIs are most common treatment for anxiety disorders

efficacy can be prevented by tryptophan depletion

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15

5-HT and Pain

descending modulatory system originating in the PAG

PAG synapses on raphe magnus » dorsal horn

inhibits ascending pain info going to cortex by synapsing onto dorsal horn neurons

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16

serotonin hypothesis of depression

low 5-HIAA

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