1. Neurotransmitters Neuropeptides Amines Amino acids Opioid peptides
Enkephalins (ENK)
Endorphins (END)
Peptide Hormones
Oxytocin (Oxy)
Substance P
Cholecystokinin (CCK)
Vasopressin (ADH)
Neuropeptide Y (NPY)
Hypothalamic Releasing Hormones
GnRH
TRH
CRH
Amines
Quaternary amines
Acetylcholine (ACh)
Monoamines
Catelcholamines
Epinephrine (EPI)
Norepinephrine (NE)
Dopamine (DA)
Indoleamines
Serotonin (5-HT)
Melatonin
Amino acids
Gamma-aminobutyric acid (GABA)
Glutamate (GLU)
Glycine
Histamine (HIST)

2. 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

3. 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

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

5. Postsynaptic Drug Actions

6. Illegal Drug Use in the U.S.
Marijuana
Cocaine
Crack
Amphetamines
Heroin

7. Marijuana #1 most widely used illegal drug in US from cannabis sativa
mild hallucinogen
brain has cannabinoid receptors (CB1)
cerebral cortex
hippocampus
basal ganglia
cerebellum
endogenous NTs are:
Anandamide
2-arachidonylglycerol (2-AG)
oleamide
THC is active ingredient
causes
memory loss
impaired tracking ability
lung damage
anxiety or paranoia
Amotivational syndrome
Gateway drug?

8. Cocaine #2 most popular illegal drug in US
from coca leave in South America
CNS stimulant
is addictive
blocks reuptake of DA, NE, and 5-HT
creates
stereotypic behaviors
nail biting/teeth grinding
pacing
an irregular heartbeat
arterial spasms
seizures
cardiac failure
has a synergistic effect with alcohol

9. Opiates Opium, Heroin, and Morphine CNS depressant is very addictive
human brain has opiate receptors
limbic system
hypothalamus
locus coeruleus
periaqueductal gray
endogenous NT are
endorphins
enkephalins
dynorphins
causes
analgesia/pain suppression
down-regulation of receptors
can lead to death by overdose

10. Hallucinogens LSD, Mushrooms acts as a 5-HT2 agonist causes
vivid images in the absence of input
geometric forms
meaningful images
separation from the body
similar effect as in
oxygen loss
sensory deprivation
can lead to “Bad Trips”
paranoia
depression
confusion

11. Ecstasy (MDMA) MDMA : 3-4 methylenedioxymethamphetamine is related to
Mescaline
MDA
methamphetamine.
it prompts nerve cells to release a flood of serotonin.
bring about the increased awareness of
emotion
intimacy
self-confidence
The ensuing chemical low tide could explain the depression users describe when they are coming down.
damages serotonin cells
damages dopamine cells

12. Ecstasy (MDMA)
Earlier animal studies had shown that repeated ecstasy use damages the serotonin brain cells, which help to regulate mood and behavior.
This image shows that serotonin axons are destroyed in a squirrel monkey after a single dose of MDMA.

13. Ecstasy (MDMA) Control Users
BRAIN CHANGES appear prominently in positron emission tomography (PET) scans of Ecstasy users as well as people who abstain. Drug users (right), though, have far less serotonin activity, as is indicated by the dark areas, compared to the controls (left). New studies show that this difference may contribute to permanent brain damage.
Serotonin Activity

14. Alcohol CNS Depressant is a great inhibitor causes
slowing of brain activity that controls reason
slowing of reaction time
depression of respiration
increase in aggressiveness
increase in risk of digestive tract cancers
increase in heart disease
decrease in sex drive
memory loss
depression
cirrhosis of the liver
fetal alcohol syndrome
brain cell death

15. Models of Addiction Moral Model Disease Model
Physical Dependence Model
Reward Model

16. Intra-Cranial Self-Stimulation
ICSS:
Electrodes are
placed in the
Medial Forebrain
Bundle (MFB)

17. Reward Pathway Ventral Tegmental Area (VTA) to
Nucleus Accumbens via the
Medial Forebrain Bundle and then to
the Prefrontal Cortex

18. Drug Addiction
Initially the CREB protein dominates leading to Tolerance and the feeling of discomfort with the absence of the drug
But the CREB protein falls after a few days if drug use discontinues
But Delta fosB stays elevated for weeks after the discontinued use of the drug leading to Drug Sensitivity

19. Drug Tolerance
During drug use VTA cells are stimulated and release Dopamine triggering the reward circuit
Dopamine binds the receptors of the Nucleus Accumbens and increases cAMP and Ca2+
ion concentrations
cAMP and Ca2+ activate the CREB protein
CREB activates the Dynorphin gene to make the Dynorphin protein
The Dynorphin protein is released back on the VTA where it inhibits Dopamine release depressing the reward circuit and causing the user to need more drug for the same high

20. Neurobiology of Drug Addiction
Drug Sensitivity
Neurobiology of Drug Addiction
During drug use VTA cells are stimulated and release Dopamine triggering the reward circuit
Dopamine stimulates the formation of Delta fosB
Delta fosB inactivates the Dynorphin gene and activates the CDK5 gene
The CDK5 protein stimulates dendritic spine growth in the Nucleus Accumbens
Nucleus
Accumbens
neuron
Increasing Drug Sensitivity/Addiction

21. Drug Sensitivity/Addiction
Nucleus Accumbens neurons in non-human animals:
Non-Addictive Drugs
Cocaine
Greater density of Dendritic Spines
Contributes to Drug Sensitivity (increased risk of drug relapse)
Delta fosB may be the contributing factor of increased spine growth