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Where do psychoactive drugs work?

Where do psychoactive drugs work?. The CNS Neurons and synapses Neurotransmitters. Nervous system structures. The peripheral nervous system Voluntary/sensory Autonomic Sympathetic Parasympathetic The Central Nervous System The spinal cord The brain. CNS functions.

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Where do psychoactive drugs work?

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  1. Where do psychoactive drugs work? The CNS Neurons and synapses Neurotransmitters

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

  3. 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

  4. CNS structure • Six major parts, in ascending order • Spinal cord • Myelencephalon • Metencephalon • Mesencephalon • Diencephalon • Telencephalon

  5. 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

  6. Myelencephalon and metencephalon comprise the hindbrain Major parts:Cerebellum, 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

  7. 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

  8. The diencephalon • Thalamus • Hypothalamus

  9. 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

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

  11. 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

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

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

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

  15. The latest neurotransmitters • Neurotransmitter gases • Carbon monoxide (CO) • Nitric oxide (NO) • Lipids • Anandamide

  16. 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.

  17. 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.

  18. Examples of second messengers • Cyclic adenosine monophosphate (cAMP) activates protein kinase A (PKA) • Cyclic guanosine monophosphate (cGMP) activates protein kinase G (PKG)

  19. 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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