Pharmacology
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| Modern Neuropharmacology | •Basic Science:
-Use of drugs to understand the brain
•Biomedical Science:
-Cure and treatment of mental disorders
–Understanding addiction
–Cognitive enhancers
•Behavioral Pharmacology has applications to all
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| Drug Delivery | Dose vs Dosage
Acute vs chronic
Routes of Delivery
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| Blood Brain Barrier | Body capillaries: large gaps, drugs pass freely
Brain Capillaries: dense, walled structure, surrounded by glial cells
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| Research Methods | •Immunocytochemistry
•In situ hybridization
•Microiontophoresis
•Molecular analysis
•Receptor binding (Immuno, Autoradiography) •Behavioral pharmacology
•Epidemiology
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| Neurotransmitters Amino Acids | •(GABA, Glutamate (Glu), Glycine(Gly)
•Excitatory vs Inhibitory
•Receptor subtypes
•GABA and inhibition
•Excitotoxicity
•Dale’s principle
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| Neurotransmitters Amines | •Ach,NE,Epinephrine,Dopamine,Histomine, 5-HT
•Receptor subtypes
•Diffuse modulatory effects: Core, small set of neurons, Widespread terminations, Diffusion out of synaptic cleft
•modulate other transmitters in both directions
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| Neurotransmitters Neuropeptides | •Peptide Hormones: Oxytocin, SubsP, CCK, Vasopressin, Neuropeptide Y, Hypothalamic releasing hormones
•Opiate Peptides: Enkephalins, endorphins, dynorphins
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| Neuropeptide Characteristics | •Neuropeptide transmitters colocalize with each other and with amine and amino acid neurotransmitters
•synthesized in the nucleus and transported to the terminals
•Stored in secretory granules instead of synaptic vesicles
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| Precursors and Enzymes: Ach | –Acetyl CoA
–Choline
–Chat
–Acetyl cholinesterase
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| Precursors and Enzymes: Serotonin | –Tryptophan
–Tryptophan hydroxylase
–5HTP
–Dopa-L-decarboxylase
–MAO
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| Neurotranmitter Criteria | •Exists in presynaptic terminals
•Presynaptically synthesis
•Released because of action potential
•Postsynaptic membrane has receptors
•Synapse stimulation produces response
•Blockade of release shuts down or substantially alters synaptic function.
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| Basal Forebrain Projections | •Septohippocampal
•Septocortical
•Septoamygdala
•Midbrain projection to the thalamus
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| Definitions | •Selectivity
•Specificity
•Potency
•Affinity
•Addiction
•Dependence
•Tolerance
•Insensitivity
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| Law of Mass Action | D + R <-> DR
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| Definition of Doses | •ED50: Median Effective Dose
•LD50: Median Lethal Dose
•CD50: Median Convulsive Dose
•KD50: Measure of affinity
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| Drug Abuse: Cannabinoids | Cannabinoid receptors are widely distributed in the brain especially in the motor control pathways, hippocampus, and cortex
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| CNS Depressants | •Include alcohol, barbituates and barbituate like substances, and anxiolytics(benzodiazepines)
•Used to treat sleep disorders, pain, anxiety
•Can cause physical dependence.
•Brain effects are primarily GABA-ergic.
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| Anxiolytics | •Prevalence of anxiety disorders
•Self-medication: alcohol, barbiturates
•Discovery of specific benzodiazepine receptor on GABAacomplex
•Valium: potentiates GABA effects (useful: potential drug for epilepsy).
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| Models of Drug Use | •The moral model
•The disease model: no explanation of how drug use commences
•The physical dependence model: but lack of physical withdrawal effects with some drugs
•The cellular effects model
•The positive reward model
•Animal research model
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| Positive Rewards Model | Cocaine elevates synaptic DA concentrations leading to the euphoric properties of the drug. After use, DA decreases to below normal levels causing dysphoria and cravings.
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| Biological psychology and treatments for drug abuse | •Opiates and naltrexone, methadone
•Alcohol and Antabuse
•Benzodiazepinesas treatment for withdrawal symptoms
•Nicotine gum and patches.
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