Where do psychoactive drugs work

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Where do psychoactive drugs work?

• The CNS
• Neurons and synapses
• Neurotransmitters

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Nervous system structures

• The peripheral nervous system
• Voluntary/sensory
• Autonomic
• Sympathetic
• Parasympathetic
• The Central Nervous System
• The spinal cord
• The brain

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CNS functions

• Inputs (sensory systems)
• Processing
• Reflexes Connecting inputs to outputs
• Thinking, feeling, remembering, and deciding
• Modulating inputs Attention and inhibition
• Outputs
• Control of muscles and glands

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CNS structure

• Six major parts, in ascending order
• Spinal cord
• Myelencephalon
• Metencephalon
• Mesencephalon
• Diencephalon
• Telencephalon

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Parts of CNS

• Myelencephalon
• Medulla Vegetative reflexes, area postrema
• Reticular Activating System begins
• Metencephalon
• Pons and cerebellum
• More of the RAS, including
• Raphe nuclei (8) serotonin (5-HT) source
• Locus ceruleus norepinephrine (NE) source

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Myelencephalon and metencephalon comprise the
hindbrain

• Major partsCerebellum, medulla, and pons
• Drug effects Life support in medulla, vomiting
  reflex center (area postrema), vagal reflex
  centers and meditatio mortis
• Arousal via the reticular activating system
• Mood, eating, and sleep via the raphe
• Fear and PTSD via the locus ceruleus

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More parts

• Mesencephalon or midbrain
• Tectum Visual and auditory reflexes
• Colliculi
• Inferior colliculi (auditory location)
• Superior colliculi (visual location and reflexes
• Tegmentum
• Periaqueductal gray (PAG) Opioid receptors
• Substantia nigra Dopamine source
• Ventral tegmental area Dopamine

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The diencephalon

• Thalamus
• Hypothalamus

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And finally

• Telencephalon
• Basal ganglia Caudate nucleus, putamen, globus
  pallidus aka corpus striatum
• Limbic system
• Cingulate cortex
• Hippocampus
• Amygdala
• Nucleus accumbens
• Cortex Frontal, temporal, parietal, occipital

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More forebrain The cortex

• Lobes of cortex Frontal, parietal, temporal,
  occipital
• The limbic lobe, especially the cingulate gyrus.
• Role in craving

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The forebrain

• Thalamus and hypothalamus
• Mesolimbic dopaminergic pathway and dopamine
  reinforcement
• The nucleus accumbens
• Limbic system
• Amygdala and hippocampus
• Basal ganglia
• Caudate nucleus, putamen, and globus pallidus
• The extrapyramidal motor system

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Neurons

• Dendrites, axon, and soma
• Synapses
• Receptors
• Ionotropic
• Metabotropic
• Gating of channels
• Voltage gating
• Neurotransmitter gating

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Neurotransmitters

• Cholinergic Acetylcholine
• Enzyme Acetylcholine esterase
• Monoamine
• Catecholamines
• Dopamine
• Norepinephrine and epinephrine
• Indole amine Serotonin
• Enzymes MAO and COMT

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More neurotransmitters

• Amino acids
• Glutamate/l-glutamate/glutamic acid
• NMDA receptors
• Enzyme GA decarboxylase
• GABA (g-aminobutyric acid)
• Neuropeptides
• Endorphins and enkephalins
• Substance P

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The latest neurotransmitters

• Neurotransmitter gases
• Carbon monoxide (CO)
• Nitric oxide (NO)
• Lipids
• Anandamide

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One more complication

• Receptor complexes may act via second messengers
• Consider the role of Ca2 It can act as a sort
  of second messenger in the post-synaptic cell
  after ionotropic activation.
• In metabotropic receptor systems, second
  messengers are inside the receiving cell.

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The role of second messengers

• Some G-protein metabotropic receptors open other
  ion channels as a result of the moving G-protein.
• Other G-protein metabotropic receptors activate
  an effector enzyme, which then activates a second
  messenger
• The second messenger in turn activates a protein
  kinase, which changes a substrate protein,
  typically through phosphorylation.

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Examples of second messengers

• Cyclic adenosine monophosphate (cAMP) activates
  protein kinase A (PKA)
• Cyclic guanosine monophosphate (cGMP) activates
  protein kinase G (PKG)

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Additional functions of tyrosine kinase
receptors neuron survival

• Mediate neurotrophic factors
• NGF trkA receptors
• BDNF (Brain-Derived Neurotrophic Factor) trkB
• NT-3 trkC
• NT-4 trkB
• Action is by mutual phosphorylation on tyrosine
  residues on each receptor inside the cell
  cytoplasm
• As a result, other protein kinases are activated
  inside the cell.

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