Transcript CNSIntro

Drug Actions in
The Nervous System
Lecture Outline
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Neurons and Membrane Potentials
Synaptic Processes and Drug Actions at
Synapses
Nervous System Organization and Key
Structures
Neurochemical Pathways and Key
Examples
Specific Examples of Synaptic Actions of
Drugs
Neurons
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Nervous systems consist of specialized
cells (neurons) for receiving, integrating
and transmitting information.
Neuron Cell Membranes
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Membrane Structure
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Semipermeable phospholipid
bilayer
Proteins
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Ion channels
Transport pumps
Receptors
Membrane Potential
Resting Membrane Potential
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Due to an uneven distribution of ions inside
and outside the cell membrane
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more positively charged ions outside,
more negatively charged ions inside
The ions responsible for the membrane
potential include
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K+, Na+, Cl-, Ca2+ and some large
molecules of amino acids
Two processes regarding ion movement
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Diffusion
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Electrostatic charges
Membranes are not permeable to ions
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specialized channels (ionophores)
Action Potential
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Depolarization
Hyperpolarization
Threshold
Voltage-gated ion
channels
Postsynaptic Potential
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Graded Potentials
Postsynaptic
Potentials
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Excitatory (EPSP)
Inhibitory (IPSP)
Neurochemical Synapse
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Presynaptic
Membrane
Postsynaptic
Membrane
Synaptic Vesicles
Synaptic Cleft
Receptor Sites
Chemical Messengers
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Hormones: released from
endocrine glands, widespread
targets.
Neurotransmitters: released from
neurons, discrete and local
targets.
Receptors: Cell structures that
receive chemical messages,
including those from hormones
and neurotransmitters.
Major Steps in Neurochemical
Synaptic Transmission
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Synthesis
Storage
Neurotransmitter Release
Receptor Activation
Deactivation
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Enzymatic Deactivation
Reuptake
Synthesis
Receptor Activation
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Ionotropic Receptors
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Involve ligand-gated ion
channels
Metabotropic Receptors
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Stimulate a cascade of
events involving G proteins
and second messengers
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interact with gated ion
channels
activate kinases, which may
influence transcription
factors and gene expression
Drug-Receptor Interactions
Drug-Receptor Interactions
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Agonists
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Competitive
Noncompetitive
Antagonists
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Competitive
Noncompetitive
Neuropharmacology
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The study of drug actions on
neurochemical and neurophysiological
processes.
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Drugs are exogenous ligands.
Drugs may activate the same receptors as
the endogenous ligands
(neurotransmitters).
Drugs may modify the actions of
endogenous ligands.
Nervous System Divisions
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The Central Nervous System
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Somatic Nervous System
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Brain and Spinal Cord
Sensory Nerves (inputs, afferents)
Motor Nerves (outputs, efferents)
The Autonomic Nervous System
(ANS)
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Sympathetic
Parasympathetic
NERVOUS SYSTEM DIVISIONS
Autonomic Nervous System
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Controls body’s internal environment
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Divisions
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Regulates involuntary functions of the
body
Sympathetic
Parasympathetic
Many psychoactive drugs
simultaneously affect CNS and ANS
Autonomic Nervous System
Autonomic Nervous System
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Sympathetic Division
 Exits Thoracic-Lumbar
region of SC
 Norepinephrine in
postganglionic synapses
 Fight-or-Flight Response
 Elevated hr, bp
 Pupil dilation
 Increased sweat gland
activity
 Dry mouth
 Increased blood flow
to muscles
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Parasympathetic Division
 Exits Cranial and Sacral
regions of SC
 Acetylcholine in
postganglionic
synapses
 Energy Conservation
 Decreased hr, bp
 Pupil constriction
 Salivation
 Gastric Secretion
NEUROTRANSMITTERS IN THE BRAIN
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Chemical Pathways
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Dopamine
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Acetylcholine
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Most widely studied neurobiological theory of
drug dependence relates to dopamine
Reduced quantities found in Alzheimer’s
patients
Norepinephrine
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Stimulant drugs may induce wakefulness
through these pathways
NEUROTRANSMITTERS IN THE BRAIN
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Chemical Pathways
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Serotonin
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GABA
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Research on weight control, aggressiveness, and
depression are centered on these chemicals
Widespread in CNS
GABA dysfunction associated with seizure disorders
Anticonvulsants are GABA agonists
Endorphins
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Involved in body’s natural mechanisms of pain relief
Other functions not well understood
Neurochemical Pathways in CNS
Acetylcholine (ACh)
Norepinephrine (NE)
Dopamine (DA)
Serotonin (5-HT)
DRUG ACTIONS IN THE BRAIN
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Possible Mechanisms of Drug Actions
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Effects of all neurons
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Some drugs (e.g., alcohol) can affect all neurons
Effects on Specific Neurotransmitter
Systems
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Different psychoactive drugs produce
different types of effects on neurochemical
transmission and on different
neurotransmitter systems
SOME PRESYNAPTIC DRUG ACTIONS
SOME POSTSYNAPTIC DRUG ACTIONS
Common Neurotransmitters
and Drug Actions
Neurotransmitter
dopamine
type of effect
inhibitoryexcitatory
GABA
inhibitory
serotonin
inhibitory
acetylcholine
excitatoryinhibitory
endorphins
inhibitory
CNS changes
euphoria
agitation
paranoia
sedation
relaxation
drowsiness
depression
sleep
relaxation
sedation
mild euphoria
excitation
insomnia
mild euphoria
block pain
slow respiration
drugs of abuse
amphetamines,
cocaine
alcohol,
Valium-type
barbiturates
LSD
tobacco,
nicotine
narcotics