Chapter 4 Flashcards by Jessica Mahan

Life Cycle of a Neurotransmitter

Synthesis from precursor chemicals

Storage into synaptic vesicles

Release (Exocytosis) from presynaptic terminal
–Triggered by action potentials and the opening of voltage gated Ca2+ channels
–Modulated by presynaptic facilitation and inhibition

Receptor binding
–Ionotropic or metabotropic

Deactivation
–Diffusion, reuptake or enzymatic degradation

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Categories of Chemical Messengers

Neurotransmitters: communicate locally across the synapse

Neuromodulators: communicate with target cells more distant than the synapse by diffusing away from the point of release

Neurohormones: communicate with target cells at great distance, often by traveling through circulation

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Neuromodulators

Include serotonin, Dopamine and acetylcholine

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The Endocrine System

Hormones are secreted into bloodstream by the endocrine glands

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Gonads

Secrete sex steroid hormones
—estrogen and progesterone in females and androgens in males

Puberty: secondary sexual characteristics

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Neurotransmitter Defined

Must be synthesized within neuron
Released in response to AP and has measurable effect on postsynaptic cell
Can duplicate action experimentally
Mechanism must exist for termination of effect

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Acetylcholine (Ionotropic and Metabotropic)

Nicotinic receptor: Ionotropic
Gates Na+, excitatory
Found at the neuromuscular junction, autonomic nervous system

•Muscarinic receptor: Metabotropic
•Found predominantly in the brain
•Can be excitatory or inhibitory
(Amanita muscaria is a type of mushroom)

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Cholinergic system (Acetylcholine)

Functions: Attention, Learning and memory
Deterioration implicated in Alzheimer’s disease

Basal Forebrain, Pons, and Midbrain

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Catecholamine

Catecholamines are Monoamnines.

Dopamine, Norepinephrine and Epinephrine

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Catecholamine Synthesis

Tyrosine> l-dopa> Dopamine> Norepinephrine> Epinephrine

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Dopamine

Receptors:
−Metabotropic
−Can be excitatory or inhibitory

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Dopaminergic system (Dopamine)

Substantia Nigra
Ventral Tegmental Area
Basal Ganglia
Frontal Lobe
Limbic system:
Nucleus Accumbens, Amygdala, Hippocampus

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Systems of Dopaminergic Neurons

Mesolimbic system: projections from ventral tegmental area (VTA) to nucleus accumbens, hippocampus, and amygdala
•Function: reward
•Implicated in Addiction

Mesocortical system: projections from VTA to prefrontal cortex
•Functions: planning, problem solving
•Implicated in Schizophrenia

Nigrostriatal System: projections from substantia nigra to basal ganglia
•Function: control of movement
•Implicated in Parkinson’s disease

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Serotonin (5-HT)

Synthesis: Tryptophan

Receptors:
−Metabotropic
−Can be excitatory or inhibitory

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Serotonergic system (Serotonin)

Functions: Sleep, arousal, appetite, mood
Implicated in anxiety and depression

Raphe Nuclei

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Glutamate

Principle excitation transmitter in the CNS

Ionotropic or Metabotropic postsynaptic receptors

Two principle ionotropic receptors:
•AMPA
•NMDA

AMPA receptor gates Na+, excitatory

NMDA receptor is unique among receptors, requiring both ligand (NT) binding and membrane depolarization

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Principle excitatory transmitter in the CNS

Glutamate

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This receptor is unique among receptors, requiring both ligand (NT) binding and membrane depolarization

NMDA receptor
The N-methyl-D-aspartate receptor, a glutamate receptor, is the predominant molecular device for controlling synaptic plasticity and memory function. The NMDAR is a specific type of ionotropic glutamate receptor.

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Principle inhibitory NT in the CNS

GABA

Principle inhibitory NT in the CNS

•GABAA (Ionotropic)
–Gates Cl-, inhibitory (influx)
–Multiple binding sites

•GABAB (Metabotropic)
–Gates K+, inhibitory (efflux)

Pituitary peptides

–Oxytocin: maternal care; bonding

Opioid peptides

–β-endorphin: reduces pain, produces

feelings of well being (e.g., runner’s high)

Gaseous Neurotransmitters

(Rare)

•Nitric Oxide
–Diffuses through membrane independent of vesicle
–Retrograde transmitter influencing presynaptic neuron’s release

Drug

any substance that alters function of the synapse, in the body (PNS) or brain (CNS)

–Agonist: mimics or enhances the effect of a neurotransmitter

–Antagonist: blocks or decreases the effect of a neurotransmitter

Drug Routes of Adminstration

From fastest to slowest: - Injection - Inhalation - Oral - Topical

Individual Differences in Drug Effects

- Gender - Body Weight - Genetics - Experience

Agonist

mimics or enhances the effect of a neurotransmitter. ``` −Increase synthesis −Promote release −Block reuptake or degradation −Block presynaptic autoreceptors −Activate postsynaptic receptor ```

Antagonist

blocks or decreases the effect of a neurotransmitter. ``` −Reduce synthesis −Prevent storage −Block release −Activate presynaptic autoreceptors −Block postsynaptic receptor ```

Sites of Drug Action

1. Synthesis 2. Storage 3. Release 4. Receptor Interaction 5. Inactivation 6. Reuptake 7. Degradation

Psychoactive Drug

Any drug with psychological effect - passes through blood brain barrier to directly affect brain –Drugs of abuse –Therapeutic drugs

Classes of Psychoactive Drugs

Opiates –Morphine, Heroin, Codeine, Endorphins Depressants –Alcohol, barbiturates, Quaaludes, Valium Stimulants –Tobacco, caffeine, cocaine, methamphetamine Psychedelics –LSD, PCP, Psilocybin, Ecstasy Marijuana

Depressants

Drugs that reduce CNS activity –Sedative (calming) effects –Anxiolytic (anxiety-reducing) effects –Hypnotic (sleep-inducing) effects

Blood Alcohol Content (BAC)

``` Factors influencing BAC: –Number/type of drinks –Weight –Gender –Genetic Background ```

Neurochemical Effects of Alcohol

GABAA receptor agonist: −Antianxiety / sedative effects −Motor impairment NMDA receptor antagonist: –Memory problems Dopamine receptor agonist: –Euphoric qualities

Stimulants

``` Drugs that increase CNS activity –Increase Heart Rate –Increase Respiration –Increase Blood Pressure –Increase arousal –Increase alertness –Elevate mood ```

Cocaine

``` Extracted from coca plant, can be snorted, inhaled, or injected to produce: –Euphoria –Decreased appetite –Increased alertness –Relieved fatigue ```

Methamphetamine

Synthetic drug, can be snorted, inhaled, or injected to produce effects similar to cocaine

Cocaine/Meth Binding Sites

Mesolimbic system Reward Pathway: –Ventral Tegmental Area (VTA) releases dopamine onto the Nucleus accumbens

Neurochemical effects of Cocaine

Blocks dopamine reuptake into VTA presynaptic neurons | More dopamine is available at the NA postsynaptic receptors

Neurochemical effects of Methamphetamine

Stimulates dopamine release from VTA Blocks dopamine reuptake More dopamine is available at the NA postsynaptic receptors

Psychedelic Drugs

``` Cause perceptual & cognitive distortions Serotonin receptor agonists: –Lysergic acid diethylamide (LSD) –PCP (Angel’s dust) –Psilocybin (Mushrooms) –MDMA (Ecstasy) ```

Neurochemical effects of Ecstasy

Increases serotonin release and blocks reuptake More serotonin is available to bind postsynaptic receptors Less serotonin is available for release and autoreceptor activation decreases synthesis and release even further Serotonin levels decrease after use

Mesolimbic system

projections from ventral tegmental area (VTA) to nucleus accumbens, hippocampus, and amygdala •Function: reward •Implicated in Addiction

Mesocortical system

projections from VTA to prefrontal cortex •Functions: planning, problem solving •Implicated in Schizophrenia

Nigrostriatal System

projections from substantia nigra to basal ganglia •Function: control of movement •Implicated in Parkinson’s disease

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Chapter 4 Flashcards

Psychopharmacology: Life cycle of a Neurotransmitter Types of Neurotransmitters Drug effects Drug actions at the synapse Effects of psychoactive drugs

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