Brain Chemistry

1. Brain Chemistry An exploration of drugs and poisons and their effect on the brain

2. Psychoactive Drugs • Drugs that act on the central nervous system to: • Alter consciousness • Modify perceptions • Change moods • More than 200 million people world wide abuse drugs • 20% of high school seniors report using pot in the last 30 days

3. Categories of Illegal Drugs • Stimulants • Increases activity of sympathetic nervous system • Euphoria, increased alertness • Depressants • Slow down activity in all parts of the central nervous system • Hallucinogens • Alter perception of reality • Off-prescription drugs • Abuse of prescription drugs

4. Stimulants Cocaine Amphetamines (speed) Methamphetamines (crystal meth) Caffeine Nicotine Off-prescription drugs Oxycontin Ritalin Hallucinogens LSD Psilocybins (mushrooms) MDMA (Ecstasy) Phencyclidine (PCP, angel dust) Depressants Heroin, morphine Cannabis (pot, hash) GHB (gamma hydroxy butyrate) alcohol Examples of Drugs in Each Category

5. Use of Psychoactive Drugs • Tolerance—need to taking increasing amounts of the drug to get the same effect • Physical dependence—physiological need for the drug to avoid withdrawal symptoms • Psychological dependence–strong desire to repeat drug use for emotional reasons, like stress reduction • Addiction–overwhelming need to use a drug and secure its supply

6. What substances are most addictive?

7. What drug poses the biggest acute health risk?

8. What do drugs do in your body? • They affect how signals are passed between brain cells

9. Electrical pulse moves along axon • At end of axon pulse triggers release of neurotransmitters from vesicles in terminal button into synapse • Neurotransmitters attach to selective receptors on dendrite of next cell (like lock and key) • Ion channels open generating action potential (electrical pulse) • Neurotransmitters are reabsorbed by axon

10. How are electrical pulses created? • More Na+ outside, more K+ inside cell regulated by cell membrane • Ion channels—large protein ”gates” in the membrane for the Na+ and K+, negative ions can’t move through gate • At rest, membrane is polarized, inside is slightly negative (-70 mV — resting potential) • Pulse is created when gates open and ions are allowed to move across the membrane

11. Opening the Gates • Two ways to open the gates • Use a neurotransmitter “chemical key” to change protein molecular structure and open channel • Occurs in the synapse • Be embedded in a region of the membrane that changes its polarity • Occurs along the axon • Myelin sheath speeds up the transmission

12. How are electrical pulses created? • Turn on • Activation of the gates opens Na+ channels, Na+ rushes in depolarizing membrane • 1 ms long • Action potential rises locally • Next section of neuron is activated • Turn off • Na+ channels close, K+ channels open so K+ rushes out of cell • Charge balance restored • Return to resting potential

13. Watching the pulse go by

14. Neurotransmitters control the gates at the synapse • More than 50 identified, 6 main ones • Excitatory, inhibitory or both • Excitatory makes it easier to trigger the neuron • Inhibitory makes it harder to trigger the neuron • Receiving neuron integrates messages from many sending neurons • Triggering an action potential takes signals from • multiple neurons • fewer neurons sending many repeat messages

15. What psychoactive drugs and poisons do • Interfere with functioning of neurotransmitters • Agonist • Mimics or increases neurotransmitter’s effects • Blocks neurotransmitter’s reuptake so it hangs out in the synapse • Antagonist • Blocks neurotransmitter’s effects by occupying receptor sites but NOT opening channel • Diminishes neurotransmitter’s release from the vesicles in the terminal bud

16. An example: acetylcholine

17. Ion Channel/Receptor

18. Opening the Ion Channel

19. Brain Structure • Brain is 50% lipid unlike any other organ • Mostly membranes in neurons and myelin sheath • Blood brain barrier provides chemically protected environment • Neurotransmitters can function differently than they do elsewhere in the body • Most neurotransmitters are made of non-essential amino acids • The brain can make them

20. Blood Brain Barrier • Blood brain barrier—keeps many blood borne chemicals out • Permeable to H20, O2, glucose, CO2, small lipid-soluble substances, small electrolytes • Active transport for amino acids

21. Main Neurotransmitters • Acetylcholine • Controls action of muscles, learning, memory • Low acetylcholine leads to Alzheimer’s • GABA • Keeps neurons from firing (inhibitor) • Low GABA leads to anxiety • Norepinephrine • Inhibits central nervous system • Excites heart muscle, intestines • Low norepinephrine leads to depression • High norepinephrine leads to hyperactivity • Cocaine and amphetamines rapidly increase levels of norepinephrine

22. Main Neurotransmitters • Dopamine • Inhibitory • Controls voluntary movement, sleep, mood, attention, learning • High levels are associated with schizophrenia • Stimulant Drugs (cocaine, amphetamines) activate dopamine receptors • Serotonin • Inhibitory • Regulation of sleep, mood, attention, learning • Low levels are associated with depression • Prozac increases levels of serotonin • Endorphins • Neurohormone—17 amino acid peptide • Stimulate firing of neurons • Shield body from pain, elevate pleasure • Morphine, heroin mimic action of endorphins

23. Neurotransmitters serotonin acetylcholine dopamine GABA norepinephrine

24. Your Patchwork Brain • Dopamine is made in only in cell bodies in certain parts of the brain • The axons of these cells connect to other specialized brain regions

25. DrugNeurotransmitter Links

26. DrugNeurotransmitter Links

27. DrugNeurotransmitter Links

28. Stimulants caffeine amphetamine cocaine nicotine

29. What drugs and poisons do Example: • Acetylcholine neurotransmitter involved in muscle action, learning and memory • Black widow spider venom causes huge release of acetylcholine leading to violent muscle spasms • Curare blocks acetylcholine receptors, paralyzing victims • Nicotine stimulates acetylcholine receptors so neuron fires more easily, making you feel more alert

30. Cocaine in the Brain • Cocaine concentrates in regions of the brain with dopamine synapses • Blocks dopamine re-uptake channel in transmitting neuron • More dopamine remains in the synapse, so more dopamine receptors on receiving neuron remain activated • Equilibration process just like in chromatography between sticky sites and solvent • Easier to trigger receiving neuron

31. What Cocaine Does • Blocks the reuptake of the neurotransmitters: • dopamine • norepinephrine • serotonin

32. What Cocaine Does • Cocaine acts as a local anaesthethic by blocking Na+ channels so the action potential can’t move down theaxon

33. Your Brain on Cocaine Red = max glucose usage Blue=least glucose usage MRI and PET scans show that over time Cocaine users brains show less brain activity brown = max glucose usage Blue=least glucose usage

34. Long Term Effects of Cocaine Red = max glucose usage Blue=least glucose usage Normal brain Long Term Effects 10 days after last Drug use brown = max glucose usage Blue=least glucose usage 100 days after last Drug use

35. Cocaine Overdose • Large increases in blood pressure • Bleeding into the brain • Stroke from constriction of blood vessels in the brain • Breathing problems • Irregular heart beat • Dilated eyes

36. Cocaine Use in the US • According to the DEA in 2005 • 2.4% of the US population has used in the past year • 34.15 million people (14.7%) have tried it at least once • Student reports of lifetime use • 3.7% of 8th graders • 5.2% of 10th graders • 8.0% of 12th graders • Student reports of use in last 30 days • 1.0% of 8th graders • 1.5% of 10th graders • 2.3% of 12th graders

37. Cocaine Use in the US • Cocaine seizures in 2005 • 118,270 kgs X 2.2 lb/kg = 260,194 lbs • Average street price per gram is $118.74 in June 2007, 59% pure • Mid level wholesale price 1 gram pure cocaine = $70.39 • Wholesale for kg quantities or more per gram pure = $23.04 • Mid level wholesale value of seizures is more than $8 billion

38. Your Brain on Ecstasy MRI of a non-user (top) and of a chronic user 3 weeks after stopping using MDMA Brighter colors show more efficient re-uptake of serotonin Serotonin is fundamental to dealing with memory and emotions and studies like these show the possibility of long term memory impairment with drug use.

39. Your Brain on Ecstasy Amount of serotonin present in a control monkey brain given saline solution, 2 weeks after 2 doses of MDMA for four days, 7 years after 2 doses of MDMA for four days