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8/12/2019 Pharmcy Psych CNS Introduction 2013
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Cerebral cortex Frontal lobeplanning Motor Speech Somato-sensory Association Vision, Smell, Hearing
Limbic system
Hippocampuso Memory
Amygdalao Moodo Aggression
Hypothalamuso Biological needs
Midbrain Substantia nigra
o Movement Basal ganglia
o Motivation behavioro Vision/hearing relay
Brainstem Reticular formation
o Sleep/arousal Medulla and Pons
o Breathingo Blood pressure
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Spinal Cord Connects body to brain Input of peripheral information
o Pain, position, etc. Output of central message
o Movement, blood pressure,temperature
Neurotransmission
Synthesis Packaging Release Receptors Reuptake Degradation
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Amino Acid Neurotransmitters
Excitatory Glutamate
Inhibitory GABA
***Balance is essential: Toomuch glutamateseizures, Too much GABAsedative
Conditions Related to Glutamate and/or GABA
Epilepsy Addiction Stroketoo much glutamate Schizophrenia Anxiety Sleep disorders Anesthesia
Glutamate Synthesis & Packaging
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Receptors IonotropicNa & Ca
o AMPA (primary excitatory receptor transmission)o NMDA (plasticity-> memory learning)o Kainate
Metabotropic pre and posto mGluR
Reuptake Astrocytes prevents excitatory toxicity
Recycled!o Glutamate back to glutamine
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GABA Synthesis & Packaging
GABAAreceptors IonotropicCl-transportedinto post-synaptic cell hyperpolarize less likely to fire impulse
Benzodiazepines, alcohol, barbiturates, inhalants
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GABABreceptorsMetabotropicGiCan be pre- or post-synaptic
Presynaptic on other (Glu, DA, NE, 5-HT) neurons to decrease release oftransmittersfrom those neurons
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Monoamine Neurotransmitters
Catecholamineso Dopamineo Norepinephrineo Epinephrine
Serotonin (5-HT) HistamineCatecholamines
o Synthesis of ALL catecholamines
Tyrosine Hydroxylase (TH) rate limiting enzyme in formation ofDopamine.
Degradation dont need to know the broken down metabolites Monoamine Oxidase (MAO)BOTHmonoamines and Catecholamines Intracellular (mitochondria)Extracellular (in synapse)
Catechol-O-methyl transferase (COMT)ONLYCatecholaminesExtracellular only (in synapse)Only catecholamines
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Dopamine
Cell bodies in only two places VTAmotivation, reward, and attention
o Addiction Substantia nigramotorlearning and execution
o Movement disordersParkinsons Disease Synthesis
o Rate limiting enzyme is THo If want more dopamine must give Dopa
Packaging Vesicular monoamine transporter (VMAT) ALL monoamines use the same
transporter
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Synaptic Transporter/Reuptake 1removal from synapse
Dopamine transporter (DAT) Vesicular
Vesicular monoamine transporter Degradation MAO/COMT Dopamine
MAO (intracellular and synaptic) COMT (synaptic only)
Receptors D1 Family (D1, D5)
o Coupled to Gs (s) stimulatory D2 Family (D2, D3, D4)
o Coupled to Gi/Go (i) inhibitoryo Presynaptic autoreceptorsinhibit dopamine releasenegative feedbacko Postsynaptic
Circuitry VTAproject to limbic (nucleus accumbens, amygdala, hippocampus) and cortex
o Motivated decisionsseeking reward Substantia nigraproject to dorsal striatum
o Motormovement Diseases/Conditions
Parkinsons Substance Abuse Mood disorders
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How to regulate Dopamine Synthesis
Increase Dopa VMAT
Decrease vesicular Receptors
Block D1R/D2R Degradation
Increase/decrease COMT/MOA Reuptake
Block DATNorepinephrine catecholamine
Cell bodies in only two places Locus ceruleus (LC) Brainstem
Projections to: cerebral cortex, thalamus,amygdala
Functions: sleep/wake, attention (ADHD),negative memories (fear, anxiety, PTSD),
Mood, Depression
Synthesis From DA (dopamine hydroxylase)
Vesicular Packaging VMAT
Degradation MAO (intracellular and synaptic) COMT (synaptic only)
Synaptic transporters 1removal from synapse
o NorEpinephrine Transporter (NET)o Reuptake NET
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Receptors 1/ Gq
stimulatory
2/ Gi
inhibitory
o Presynaptic autoreceptorso Postsynaptic
/Gs
stimulatory Circuitry
Locus ceruleus (LC), brainstem Projections to cortex, amygdala,
thalamus
Diseases/Conditions Cognition ADHD Depression PTSD
Epinephrine
Found in very few neurons in medulla Function: respiration regulation
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Serotonin (5-HT+)monoamine NOT catecholamine
Cell bodies primarily in raphe Several hundred thousand neurons are 5-HT+
Project to limbic forebrain, cortex, striatum and DA neurons Attention, sleep/arousal, emotion and mood
Especially depressionSynthesis
From tryptophan (tryptophan hydroxylase) Degradation
MAO(intracellular and synaptic) Transporters
Vesicularo Vesicular monoamine transporter (VMAT)
Synaptic1removalfrom synapseo Serotonin transporter (SERT)
Receptors
13 different receptors identified (12metabotropic, 1 ionotropic)
5HT1D (pre) and 1A/Gi(post)autoreceptors inhibit
o Migraine (agonists) 5HT2A/ Gq
o Antipsychotics (antagonists)excitatory
5HT3ionotropico Anti-nausea (antagonists)excitatory
Circuitry Cell bodies in cerebellum, brainstem Projections to cortex, limbic, midbrain
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Diseases/Conditions Depression Antipsychotics Migraines Obesity/Weight Loss
Acetylcholine
Cell bodies in forebrain and brainstem Interneurons in striatum
o movement Project to limbic forebrain, cortex,
striatum
Cognition, movement, reward Synthesis
From choline and acetyl CoAo Choline Acetyltransferase (ChAT)
Degradation AChE(intracellular and synaptic)
Transporters Vesicular (VT)
o Vesicular acetylcholine transporter SynapticCholine only (NOT ACh)
o Choline transporter Receptors
Muscarinico M2/Gi( pre and post)o M1/Gq(post)
Nicotinico Ionotropic
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Diseases/Conditions Alzheimers Parkinsons Antidepressants
HistamineMonoamine Synthesis
HistadineHistamine Physiological Function
Sleep/arousal Feeding Cognition