Spring 2012 Happy Losar

Dr. Andre Ragnauth, Ph.D. Course Director SDSBE CCNY

the brain

Cortex

Neurons

Santiago Ramn y Cajal (1852 1934)

Spanish pathologist,histologist, neuroscientist, and Nobel laureate. His pioneering investigations of the microscopic structure of the brain were original; he is considered by many to be the father of modern neuroscience. He was skilled at drawing, and hundreds of his illustrations of brain cells are still used for educational purposes today.
http://en.wikipedia.org/wiki/Santiago_Ram%C3%B3n_y_Cajal

Cerebellum Cortex

Purkinje cells

Synaptic connections

A Neuron

Cartoon of interactions at a chemical synapse

Structure of a typical chemical synapse

Criteria for a Neurotransmitter

Localization
A putative neurotransmitter must be localized to the presynaptic

elements of an identified synapse and must be present also within the neuron from which the presynaptic terminal arises.

Release
The substance must be shown to be released from the presynaptic

element upon activation of that terminal and simultaneously with depolarization of the parent neuron.

Identity
Application of the putative neurotransmitter to the target cells must

be shown to produce the same effects as those produced by stimulation of the neurons in question.

Steps in Synaptic Transmission That Are Affected by Drugs

Steps in Synaptic Transmission That Are Affected by Drugs

Cathecholamines
Dopamine (DA) Precursor of norepinephrine Biological activity in the central nervous system and in the periphery Norepinephrine In the brain and in the sympathetic neurons

Epinephrine Formed from norepinephrine Released by the adrenal gland Stimulates receptors in several organs

Dopaminergic Pathways in the Brain

Dopaminergic Projection Systems

Mesolimbic tract

Nigrostriatal tract

Mesocortical tract

http://www.beautifulfunnysadandtrue.com/how-do-you-say-dopamine-in-chinese/

Dopamine (DA) Neurons

Nigro-striatal dopamine

neurons
Cell bodies are in the

substantia nigra Project to striatum Part of the extrapyramidal motor system

Motor balance, gait and muscle coordination and control

Die (degenerate) in

Parkinsons disease

Dopamine Neurons
Hypothalamic dopamine

neurons (tuberoinfundibular
pathway)

Project from the

hypothalamus to the pituitary gland Also project to the spinal cord

Controls the secretion of

certain hormones
prolactin

Dopamine Neurons
Mesocorticolimbic

dopamine neurons
Cells bodies as in the

ventral tegmental area (VTA) Project to the nucleus accumbens, the frontal cortex and the amygdala

Involved in reward and

reward seeking behaviors

of abuse

Targets for many drugs

Dopamine Synthesis and Storage in nerve terminals

Cell Body (VTA)

Projects to

DA
Nerve terminal (nucleus accumbens)

Dopamine storage and release

Dopamine release and recovery

Dopamine and Cocaine

Cocaine

binds to DAT
Blocks DA

transport Increases dopamine concentrati on in the synaptic cleft

Results in

increased and prolonged activation of DA receptors

Synapse: Dopamine

DA reuptake pumps

Dopamine binding to receptors and uptake pumps in

DA

the nucleus accumbens

DA receptor

http://www.nida.nih.gov/pubs/teaching/largegifs/slide-12.gif

Synapse: Dopamine + Cocaine

Cocaine binding to uptake

DA

pumps: inhibition of dopamine uptake

DA receptor

http://www.nida.nih.gov/pubs/teaching/largegifs/slide-13.gif

Synapse: Dopamine + Cocaine = postsynaptic effects

Increased cAMP produced

in postsynaptic cell

cAMP

http://www.nida.nih.gov/pubs/teaching/largegifs/slide-14.gif

Dopamine and Cocaine

Cocaine binds to

DAT Blocks DA transport Increases dopamine concentration in the synaptic cleft

Results in increased

and prolonged activation of DA receptors

http://schizophreniasymptoms.net/dopamine-receptors/

Dopamine and Amphetamine

Competes with DA for

the DAT
Transported into the

DA containing vesicles by VMAT

Inhibits MAO

Displaces DA from the

vesicles

MAO and antidepressants

Blocks the

degradation of DA
Used to

treat clinical depression and panic disorders

MAO Mono-Amine Oxidase

http://www.viewzone.com/dopamine.html

Norepinephrine (NE)

NE neurons are also part of the sympathetic nervous system

Fight or flight

response
NE neurons are

contained in ganglia (small mass of nerve tissue containing the cell bodies of neurons) and these neurons send long nerve fibers to the target tissues.

Actions of NE
Supply many tissues to cause excitatory responses:
Increase excitability of cardiac muscle and heart rate Constrict blood vessels causing an increase in blood

pressure Relax airways making it easier to breathe Dilate pupils Stimulates secretion epinephrine from the adrenal gland Stimulate glucose production by liver

Inhibits the gastrointestinal tract Inhibits salivary secretion

NE &drug abuse

Cocaine blocks NET

Contributes to

increased attentiveness, loss of appetite and lack of sleep

Amphetamine

transported by the NET, taken up into the vesicles

Same effects

Some

antidepressants block NET

Cocaine & Amphetamine: Psychomotor Stimulants

Both increase sympathetic nervous system signaling to

target tissues
Increased heart rate Increased blood pressure

Increased respiration
Increased pupil dilation Inhibition of gastrointestinal tract

Indolamines
Serotonin (5HT) Derived from Tryptophan Biological activity in the GI tract, blood platelets & the central nervous system. Regulates mood, appetite & sleep Melatonin Found in animals, plants & microbial life Regulates circadian rhythms Potent antioxidant & protector of DNA

Serotonin (5-HT) in the brain

Synthesis of Serotonin (5-HT)

Release and recovery of 5HT at the synapse

5-HT and MDMA (ecstasy)

MDMA
causes the release of

the neurotransmitter serotonin. blocks the reuptake of serotonin by the synaptic terminal that releases it. depletes the amount of serotonin in the brain.

5-HT and LSD (acid)

LSD mimics serotonin during the transmission process but does

not cause suppression

lead to hallucinations, visual after-images, distortions of

perception and eventually paranoia

LSD molecules are reabsorbed by the neuron for repeated

"flashback" activity and persistent perceptual distortion

Can get flashbacks up to a year after use

Cells of the associate visual cortex are particularly susceptible LSD may be a last resort treatment for extreme depression

5-HT - targets for a variety of therapeutic drugs

Potential Changes Drugs can have on Neurotransmitters

Change in neurotransmission increase the number of impulses Release neurotransmitter from vesicles with or without impulses Effect on neurotransmitter release or availability increased neurotransmitter release increased neurotransmitter release Drug that acts this way

nicotine alcohol opiates Amphetamines methamphetamines Nicotine Cocaine amphetamine LSD caffeine

Release neurotransmitter in increased neurotransmitter response to impulses release Block reuptake more neurotransmitter present in synaptic cleft

block receptor with another No change in molecule neurotransmitter release or neurotransmitter cannot bind to its receptor on the post synaptic neuron

Drugs and Reward

http://learn.genetics.utah.edu/content/addiction/dru

gs/mouse.html http://learn.genetics.utah.edu/content/addiction/ http://www.youtube.com/watch?v=b17d_c9WANE&fe ature=related http://www.youtube.com/watch?v=GiC-UuRwZFQ