1. Chemical Messengers Autocrine Paracrine Endocrine Pheromone Allomone
self signal
Paracrine
neighbor signal
Endocrine
distant signal
Pheromone
airborne signal
same species
Allomone
different species

2. Endocrine Glands

3. Homeostasis Mechanism
Receptors
input signals
skin responds to cold
temperature
sends signal to brain
Control Center
integrating center
brain interprets temp signal
makes you shiver
Effectors
output mechanism
muscles shiver creating heat

4. Neurotransmitters Neuropeptides Amines Amino acids Opioid peptides
Enkephalins (ENK)
Endorphins (END)
Peptide Hormones
Oxytocin (Oxy)
Substance P
Cholecystokinin (CCK)
Vasopressin (ADH)
Neuropeptide Y (NPY)
Brain-derived Neurotrophic factor
Hypothalamic Releasing Hormones
GnRH
TRH
CRH
Lipids
Anandamide
Gases
Nitric Oxide (NO)
Amines
Quaternary amines
Acetylcholine (ACh)
Monoamines
Catecholamines
Epinephrine (EPI)
Norepinephrine (NE)
Dopamine (DA)
Indoleamines
Serotonin (5-HT)
Melatonin
Amino acids
Gamma-aminobutyric acid (GABA)
Glutamate (GLU)
Glycine
Histamine (HIST)

5. Acetylcholine
Synthesis
Breakdown

6. Cholinergic Synapse Choline Acetyl CoA Cholinesterase (ChAT)
Acetylcholinesterase (AChE)
Choline transporter
Vesicular ACh transporter (VAChT)

7. Cholinergic (Ach) System

8. Cholinergic Receptors
Nicotinic receptors
Muscle Type
Neuromuscular junction
Autonomic ganglia
CNS Type
Muscarinic receptors M1
CNS M2
Heart M3
Blood vessels
Lungs
Exocrine Glands M4 M5
Cholinergic Receptors
Iontotropic
metabotropic
Nicotinic ACh Receptor

9. Catecholamine Synthesis

10. Noradrenergic (NE) System

11. Noradrenergic Receptors
Alpha 1 receptors
Smooth muscle
Skin
GI tract
Kidney
brain
Alpha 2 receptors
Beta 1 receptors
Heart
kidneys
Beta 2 receptors
Lungs
Liver
uterus
Vascular smooth muscle
Skeletal muscle
Beta 3 receptors
Fat cells
Noradrenergic Receptors
All metabotropic

12. Dopaminergic Synapse Tyrosine Tyrosine Hydroxylase DOPA
Aromatic Amino Acid Decarboxylase
Dopamine Transporter
Vesicular Monoamine Transporter
D2 Autoreceptor

13. Dopaminergic (DA) System 1 Mesolimbic*
Ventral Tegmental Area (VTA)

14. Dopaminergic (DA) System 2 Mesostriatal*
Basal Ganglia

15. Dopaminergic Receptors
D1 receptors
D2 receptors
D3 receptors
D4 receptors
D5 receptors

16. Serotonin (5-Hydroxytryptamine) (5-HT)

17. Serotonergic Synapse Tryptophan Tryptophan hydroxylase 5-HTP
Aromatic l-amino acid decarboxylase (AADC)
5-HT
5-HT transporter
5-HT autoreceptor

18. Serotoninergic (5-HT) System

19. Serotonergic Receptors
5-HT1A-F receptors
CNS
Blood Vessels
5-HT2A-C receptors
PNS
GI Tract
5-HT3 receptors
5-HT4 receptors
5-HT5A-B receptors
5-HT6 receptors
5-HT7 receptors
Serotonergic Receptors
Iontotropic
Metabotropic
5-HT1B receptor

20. Glutamate Synthesis Glutamine Glutaminase Glutamic Acid Glutamate
Aspartic Acid
Aspartate

21. Glutamate Synapse

22. Glutamate Receptors AMPA receptors Kainate receptors NMDA receptors
GluA1-4
Kainate receptors
GluK1-5
NMDA receptors
GluN1
GluN2A-C
GluN3A-B
Metabotropic receptors
mGluR1-8
Glutamate Receptors
Iontotropic
Metabotropic
AMPA Receptor

23. Long-Term Potentiation (LTP)
each triangle represents a single
action potential
Slope of
the EPSP
(one characteristic measure of an action potential)
baseline response
potentiated response
Hippocampus has a three synaptic pathway
Stimulate one area (mossy fibers) and record the action potentials in another (CA1)
Stimulate multiple times to get a baseline response
Once a stable baseline is established give a brief high frequency stimulating pulse
Use the same stimulating pulse as in baseline but now see a potentiated response
This potentiated response can last hours, days, or even weeks (LTP)

24. Normal Synaptic Transmission
Glutamate Channels:
NMDA
Mg2+ block
no ion flow
AMPA
Na+ flows in
depolarizes cell

25. LTP Induction With repeated activation
the depolarization drives the Mg2+ plug out of the NMDA channels
Ca2+ then rushes in through the NMDA channels
Ca2+ stimulates a retrograde messenger to maintain LTP
Ca2+ also stimulates CREB to activate plasticity genes

26. LTP-induced Neural Changes

27. Neurobiological Changes via Learning
Dendritic changes:
Increased dendritic arborization
Increased dendritic bulbs
Synaptic changes:
More neurotransmitter release
More sensitive postsynaptic area
Larger presynaptic areas
Larger postsynaptic areas
Increased interneuron modulation
More synapses formed
Increased shifts in synaptic input
Physiological changes:
Long-Term Potentiation
Long-Term Depression

28. GABA Synthesis
Glutamate
Glutamic Acid Decarboxylase (GAD)
GABA

29. GABA Synapse

30. GABA Receptors GABAA receptors GABAB receptors GABAC receptors
Iontotropic
Metabotropic
GABAA Receptor

31. GABAA receptor properties

32. Benzodiazepines (BDZ) and barbiturates cause sedation and reduced anxiety by binding to modulatory sites on the GABA receptor complex
BDZ binding sites are widely distributed in the brain.
They are in high concentration in the amygdala and frontal lobe.
Natural differences in anxiety levels are correlated with the number of BDZ binding sites.
PET scans of patients with panic disorder show less benzodiazepine binding in the CNS, particularly in the frontal lobe.
GABA and Anxiety 32

33. The Science of Drug Action
Pharmacology: study of the actions of drugs and their effects on living organisms.
Neuropharmacology: study of drug-induced changes in nervous system cell functioning.
Psychopharmacology: emphasizes drug-induced changes in mood, thinking, and behavior.
Neuropsychopharmacology: identifies chemical substances that act on the nervous system to alter behavior. . 33

34. The Science of Drug Action
Drug action: molecular changes produced by a drug when it binds to a target site or receptor. Drug effects: The molecular changes that alter physiological or psychological functions. Therapeutic effects: the drug–receptor interaction produces desired physical or behavioral changes. Side effects: all other non-therapeutic effects. Specific drug effects: are based on physical and biochemical interactions of a drug with a target site in living tissue. Nonspecific drug effects: are based on certain unique characteristics of the individual, (e.g., mood, expectations, perceptions, attitudes, placebo effects). 34

35. Therapeutic Index Effective dose Lethal dose
dose of a drug that produces a meaningful effect in some percentage of test subjects
ED50 = effective dose for half the animals in a drug test
Lethal dose
dose of a drug that has a lethal effect in some percentage of test subjects
LD50 = lethal dose for half the animals in a drug test
Therapeutic index = LD50/ED50
Always greater than one
Most drugs have an LD1 well above the ED95 35

36. Pharmacokinetic Factors

37. 1. Drug Route of Administration

38. 2. Absorption and Distribution
Lipid Solubility
Ionization pH
Stomach Content
Gender
Other
BBB
Placenta

39. 3. Drug Binding
Drugs bind to proteins in blood, or temporarily stored in bones or fat cells (inactivating drug)
Reduces the concentration of drug at site of action
Competition of binding can alter the concentration of free active drug potentially leading to overdose
Drug is not altered by liver enzymes
Can terminate action of drugs

40. 4. Inactivation (Biotransformation)

41. 5. Excretion Organs: Products: Intestines Kidneys Lungs Sweat glands
Feces
Urine
Water Vapor
Sweat
Saliva

42. Mechanism of Drug Action
Effects on specific neurotransmitter systems:
Drugs may alter the availability of a neurotransmitter by changing the rate of:
Synthesis
Metabolism
Release
Reuptake
Drugs may activate or prevent the activation of a receptor

43. Drugs can acts as Agonists
Agonist binds and has same effect
as endogenous neurotransmitter,
channel opens
Normal receptor at rest,
channel is closed
Neurotransmitter binds
receptor and opens channel

44. Drugs can act as Antagonists
Typical antagonist binds in place
of endogenous neurotransmitter,
prevents neurotransmitter action
Non-competitive binding antagonist doesn’t
interfere with neurotransmitter binding but
still prevents neurotransmitter action

45. Presynaptic Drug Actions
8. Blockade of NT
degradation
MAO inhibitors
Prozac
Chemical Weapons

46. Postsynaptic Drug Actions