Chapter 4 Flashcards
Psychopharmacology: Life cycle of a Neurotransmitter Types of Neurotransmitters Drug effects Drug actions at the synapse Effects of psychoactive drugs
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
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
Neuromodulators
Include serotonin, Dopamine and acetylcholine
The Endocrine System
Hormones are secreted into bloodstream by the endocrine glands
Gonads
Secrete sex steroid hormones
—estrogen and progesterone in females and androgens in males
Puberty: secondary sexual characteristics
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
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)
Cholinergic system (Acetylcholine)
Functions: Attention, Learning and memory
Deterioration implicated in Alzheimer’s disease
Basal Forebrain, Pons, and Midbrain
Catecholamine
Catecholamines are Monoamnines.
Dopamine, Norepinephrine and Epinephrine
Catecholamine Synthesis
Tyrosine> l-dopa> Dopamine> Norepinephrine> Epinephrine
Dopamine
Receptors:
−Metabotropic
−Can be excitatory or inhibitory
Dopaminergic system (Dopamine)
Substantia Nigra Ventral Tegmental Area Basal Ganglia Frontal Lobe Limbic system: Nucleus Accumbens, Amygdala, Hippocampus
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
Serotonin (5-HT)
Synthesis: Tryptophan
Receptors:
−Metabotropic
−Can be excitatory or inhibitory
Serotonergic system (Serotonin)
- Functions: Sleep, arousal, appetite, mood
- Implicated in anxiety and depression
Raphe Nuclei
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
Principle excitatory transmitter in the CNS
Glutamate
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.
Principle inhibitory NT in the CNS
GABA
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
- Synthesis
- Storage
- Release
- Receptor Interaction
- Inactivation
- Reuptake
- 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
