Drug Actions in The Nervous System

Lecture Outline 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 Nervous systems consist of specialized

cells (neurons) for receiving, integrating and transmitting information.

Neuron Cell Membranes Membrane Structure

Semipermeable phospholipid bilayer

Proteins Ion channels Transport pumps Receptors

Membrane Potential

Resting Membrane Potential

Due to an uneven distribution of ions inside and outside the cell membrane

more positively charged ions outside, more negatively charged ions inside

The ions responsible for the membrane potential include

K+, Na+, Cl-, Ca2+ and some large molecules of amino acids

Two processes regarding ion movement Diffusion Electrostatic charges

Membranes are not permeable to ions specialized channels (ionophores)

Action Potential Depolarization Hyperpolarization Threshold Voltage-gated ion

channels

Postsynaptic Potential Graded

Potentials Postsynaptic

Potentials Excitatory (EPSP) Inhibitory (IPSP)

Neurochemical Synapse Presynaptic

Membrane Postsynaptic

Membrane Synaptic

Vesicles Synaptic Cleft Receptor Sites

Chemical Messengers 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

Synthesis Storage Neurotransmitter Release Receptor Activation Deactivation

Enzymatic Deactivation Reuptake

Synthesis

Receptor Activation Ionotropic Receptors

Involve ligand-gated ion channels

Metabotropic Receptors Stimulate a cascade of

events involving G proteins and second messengers

interact with gated ion channels

activate kinases, which may influence transcription factors and gene expression

Drug-Receptor Interactions

Drug-Receptor Interactions Agonists

Competitive Noncompetitive

Antagonists Competitive Noncompetitive

Neuropharmacology The study of drug actions on

neurochemical and neurophysiological processes. 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 The Central Nervous System

Brain and Spinal Cord Somatic Nervous System

Sensory Nerves (inputs, afferents)

Motor Nerves (outputs, efferents)

The Autonomic Nervous System (ANS) Sympathetic Parasympathetic

NERVOUS SYSTEM DIVISIONS

Autonomic Nervous System

Controls body’s internal environment Regulates involuntary functions of the

body Divisions

Sympathetic Parasympathetic

Many psychoactive drugs simultaneously affect CNS and ANS

Autonomic Nervous System

Autonomic Nervous System

Parasympathetic Division

Exits Cranial and Sacral regions of SC

Acetylcholine in postganglionic synapses

Energy Conservation Decreased hr, bp Pupil constriction Salivation Gastric Secretion

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

NEUROTRANSMITTERS IN THE BRAIN

Chemical Pathways Dopamine

Most widely studied neurobiological theory of drug dependence relates to dopamine

Acetylcholine Reduced quantities found in Alzheimer’s

patients Norepinephrine

Stimulant drugs may induce wakefulness through these pathways

NEUROTRANSMITTERS IN THE BRAIN

Chemical Pathways Serotonin

Research on weight control, aggressiveness, and depression are centered on these chemicals

GABA Widespread in CNS GABA dysfunction associated with seizure disorders Anticonvulsants are GABA agonists

Endorphins Involved in body’s natural mechanisms of pain relief Other functions not well understood

Neurochemical Pathways in CNS

Acetylcholine (ACh) Dopamine (DA)

Serotonin (5-HT)Norepinephrine (NE)

DRUG ACTIONS IN THE BRAIN Possible Mechanisms of Drug Actions

Effects of all neurons Some drugs (e.g., alcohol) can affect all

neurons Effects on Specific Neurotransmitter

Systems 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 type of effect CNS changes drugs of abusedopamine

GABA

serotonin

acetylcholine

endorphins

inhibitory-excitatory

inhibitory

inhibitory

excitatory-inhibitory

inhibitory

euphoria agitation paranoiasedation relaxation drowsiness depressionsleep relaxation sedationmild euphoria excitation insomniamild euphoria block pain slow respiration

amphetamines, cocaine

alcohol, Valium-type barbiturates

LSD

tobacco, nicotine

narcotics