1. E.4 Neurotransmitters and Synapses
• Please review the structure of a synapse (Fig 45.15)
E.4.1 State that some presynaptic neurons excite postsynaptic transmission and others inhibit postsynaptic transmission

2. Synaptic Transmission

3. • Most synapses occur between the axonal endings of one neuron and the dendrites or the cell bodies (soma) of other neurons • The neuron conducting impulses toward the synapse is called the presynaptic neuron • The neuron that receives and conducts the signal away from the synapse is called the postsynaptic neuron • The majority of vertebrate synapses are chemical synapses

4. • Most synapses have a synaptic cleft separating the pre- from the postsynaptic neuron • The end of the presynaptic axon contains vesicles filled with neurotransmitters

5. • With the arrival of an action potential at the end of the axon, voltage-gated Calcium ion channels open and calcium ions rapidly diffuse inward across the axonal membrane • This causes the fusion of synaptic vesicles to the axonal plasma membrane with the removal of their neurotransmitters via exocytosis into the synaptic cleft • The neurotransmitters bind rapidly to chemical-gated receptor proteins on the postsynaptic membrane resulting in depolarization or hyperpolarization of the postsynaptic membrane • If the binding of the NT permits Na+ ions to diffuse into the Post Synaptic membrane and K+ ions to diffuse out at the same time in a 2:1 ratio, the result is a depolarization of the PS membrane called and excitatory postsynaptic potential (EPSP)

6. Depolarization
• This is the response that is seen with acetylcholine (at neuromuscular junctions)

7. • Hyperpolarization causes inhibition by making it more difficult for the cell to reach threshold; no action potential occurs; important for neural control of body movements • Some neurotransmitters cause the opening of chemical-gated channels for Cl− ions which will then diffuse into the Post Synaptic cell making the inside of the cell more negative than it was at rest (Ex. -70mV to -85mV) • This hyperpolarization is called an inhibitory postsynaptic potential (IPSP)

8. • Glycine and gamma-aminobutyric acid (GABA) are inhibitory neurotransmitters

9. E.4.2 Explain how decision-making in the CNS can result from the interaction between the activities of excitatory and inhibitory presynaptic neurons at synapses
• At each synapse, an action potential arriving at a synaptic knob triggers chemical or electrical events that affect another cell
• Some neurotransmitters arriving at the postsynaptic cell may be excitatory while others arriving from different neurons may be inhibitory resulting in a depolarization, a hyperpolarization, or no appreciable change in the transmembrane potential at the initial segment

10. • The TM potential at the initial segment, therefore, represents an integration of all the excitatory and inhibitory stimuli affecting the neuron at that moment • This can best be explained by looking at the affects of certain drugs on the activities of these synapses by enhancing or inhibiting their activity • Many drugs interfere with key steps in the synaptic transmission process in the following ways: 1. they may interfere with transmitter synthesis 2. they may alter the rate of transmitter release 3. they may prevent transmitter binding to receptors

11. • some drugs affect synaptic terminals (botulinus toxin)

12. • other drugs primarily affect the postsynaptic membrane (cholinesterase inhibitors)

13. • some excitatory drugs include: caffeine, spider venom, nicotine • some inhibitory drugs include: arsenic, atropine, lipid-soluble anesthetics • the drug, whether it is a feel-good drug (amphetamines), or a depressant (antianxiety drugs), will affect the decisions that we make by changing our behavior (happy, relaxed, uninhibited, depressed, etc.)

14. E.4.3 Explain how psychoactive drugs affect the brain and personality by either increasing or decreasing synaptic transmission
• Psychoactive drugs affect the brain and personality by either increasing or decreasing synaptic transmission.
• Some act as neurotransmitters and bind to receptors for that neurotransmitter in post-synaptic membranes.
• They block the receptor, preventing the neurotransmitter from having its usual effect

15. • Some have the same effect as a neurotransmitter, but unlike the neurotransmitter, they are not broken down when they bind to the receptors, so the effect lasts much longer • Finally, some interfere with the breakdown of neurotransmitter in synapses and prolong the effect of the neurotransmitter. • Example: Elavil and Sinequan help relieve depression by prolonging the activity of norepinephrine (“feeling good” neurotransmitter) on the postsynaptic membrane by blocking its release from its receptor

16. E.4.4 List three examples of excitatory and three examples of inhibitory psychoactive drugs
Three examples of excitatory drugs are:
1. Nicotine, at low to moderate doses, is a central nervous system stimulant.
• Effects include tremors, an increase in behavioral activity, increased alertness, facilitation of memory and release of epinephrine from the adrenal glands.
• In addition to these CNS effects nicotine increases heart rate and blood pressure, inhibits stomach secretions and stimulates bowel activity.

17. • Individuals experienced in the use of nicotine report pleasure and relaxation from this drug. • Those who have never used products containing nicotine often experience nausea and vomiting and report the effects as being unpleasant. • Chronic use of nicotine leads to changes in the brain and behavior. • One of the first changes is tolerance, a decrease in the effects of nicotine. Tolerance occurs rapidly to some of the unpleasant effects, including dizziness, nausea and vomiting. • This decrease in unpleasant effects may unmask the pleasurable effects of nicotine, leading to further use of the drug.

18. • The second major change seen in response to chronic ingestion of nicotine is physical dependence. • Following chronic use, there are physiological changes that lead to a requirement for the drug. • With the development of physical dependence, further administration of nicotine is necessary to avoid a physiological disturbance. • This disturbance is known as a withdrawal (or abstinence) syndrome.

19. • The withdrawal syndrome for nicotine, although not as behaviorally overt as that for other drugs such as ethanol or opiates, is very unpleasant for chronic users. • Symptoms include confusion, anxiety, irritablility, drowsiness, dizziness, headache, nausea, disturbed sleep, increased eating and weight gain, and profound craving.

20. 2. Crack cocaine is a strong central nervous stimulant that interferes with, and causes excess amounts of dopamine in the brain. • A neurotransmitter associated with pleasure and movement, dopamine is the neurotransmitter released as part of the brain's reward system. • As a result, the psychological effects can be extremely reinforcing; after having tried crack cocaine, the user will rapidly develop an intense craving for the drug since the chemistry of the brain's reward system has been altered.

21. 3. The behavioral effects of the excitatory psychoactive drugs known as amphetamines have an effect similar to cocaine, but usually last longer. • One amphetamine is ecstasy (3,4 methylenediox ymethamphetamine or MDMA) and it usually fosters feelings of empathy, openness and caring. • Individuals want to touch and be touched by others • It lowers feelings of aggression and increases sexual behavior. • Ecstasy takes control of the chemicals that influence mood, appetite, sleep, and other important functions • The aftereffects of ecstasy include depression and irritability

22. Three examples of inhibitory psychoactive drugs are: 1
Three examples of inhibitory psychoactive drugs are: 1. benzodiazepine (Valium and Temazepam) • The behavioral effect of this inhibitory psychoactive drug is a feeling of relaxation and reduction of anxiety (depressant) • Often used to treat sleep disorders • High doses cause drowsiness, slurred speech, and loss of muscle coordination; overdoses may cause death

23. 2. cannabis (THC) (tetrahydrocannabinol) • The behavioral effect of this drug is an increased intensity of sensual perception and the feeling of euphoria and relaxation • Individuals may have an altered sense of perception and experience an inability to concentrate with impaired learning and memory; it also increases appetite • Acute or toxic affects may include mood changes such as panic attacks and paranoia

24. 3. alcohol • alcohol is said to reduce inhibitions, making people more talkative and confident; loss of self-restraint • It impairs reaction times and fine muscle coordination • In large quantities it causes loss of memory, slurred speech, loss of balance and coordination

25. E4.5 Explain the effects of THC (tetrahydrocannabinol) and cocaine in terms of their action at synapses in the brain
• THC (cannabis) travels quickly to the brain and binds to cannabinoid receptors that are concentrated in areas activating the reward system of the brain
• Cannabinoid receptors are found in areas of the brain involved in attention, memory, motor co-ordination, and other cognitive functions

26. • THC blocks GABA resulting in enhanced dopamine release (the feel-good neurotransmitter) • Normally, GABA (gamma-aminobutyric acid) is an inhibitory neurotransmitter • Since there is more dopamine in the synapse, there is increased activation of dopamine receptors resulting in increased production of cAMP inside the postsynaptic cell which alters the normal activity of the neuron

28. • Cocaine use involves inhibition of dopamine removal from synapses in areas of the brain that are rich in dopamine synapses • This occurs because cocaine binds to the dopamine uptake pumps and prevents them from removing dopamine from the synapse • The resulting rise in dopamine concentrations at these synapses is responsible for the “high” that is experienced

29. • Also, more dopamine receptors are activated causing an increase in the production of cAMP inside the postsynaptic cell resulting in many changes inside the cell that lead to abnormal firing patterns

30. E.4.6 Discuss the causes of addiction, including genetic predisposition, social factors, and dopamine secretion
• Drug dependence is characterized by impaired control over the drug, preoccupation with its use with continued use despite negative consequences, and sometimes physical dependence on the drug

31. • Physical addiction occurs when repeated use of the drug alters the reward pathways in the brain • This results in physical changes to some nerve cells in the brain • Some addictive drugs, like cocaine and THC, affect some areas of the brain similarly, i.e. by increasing dopamine concentrations (feel-good NT) in the synapse along with the activation of more dopamine receptors which will then require more of the drug, since the normal amount of dopamine secretion will no longer achieve the same result

32. • Genetically, drug addiction is more common in some families and likely involves the effects of many genes • Those with family members who have drug problems will be at greater risk for developing a drug addiction • For young people, peer pressure is a strong factor in starting to use and abuse drugs • A lack of attachment with your parents may increase the risk of addiction, as can a lack of parental supervision • Other psychological problems such as depression, ADHD, or PTSD can make an individual more likely to become dependent on drugs