Neuro Chemistry

focuses on the basic chemical composition and processes of the nervous system

is the study of compounds that selectively affect the nervous system

chemical messenger that acts as a hormone to mobilize the body for fight or flight during times of stress and as a NT in the CNS

NT found in the brain and in the PNS

fit receptors exactly and activate or block them

NT and hormones
NT: chemical released by a neuron onto a target with an excitatory or inhibitory effect
outside the CNS many of these chemicals circulate in the blood stream as hormones

drugs and toxins from outside the body

_ in the axon terminal–building blocks from food are pumped into cell via transporters (protein molecules embedded within the cell membrane)
_ in the cell body according to instruction contained in the DNA, transported on microtubules to axon terminal

at the terminal the action potential opens voltage sensitive Ca2+ channels, Ca2+ enters the terminal and binds to the protein calmodulin forming a complex
complex causes some vesicles into empty the synapse and others get ready to empty their contents

after being released, the NT must diffuse across the synapse and activates receptors on the postsynaptic membrane
autoreceptors–“self-receptor” on the presynaptic membrane that responds to the transmitter that the neuron releases

embedded membrane protein with 2 parts–a binding site for a NT and a pore that regulates ion flow to directly and rapidly change membrane voltage

embedded membrane protein with a binding site for a NT but no pore
linked to a G protein that can affect other receptors or act with second messengers to affect other cellular processes

belongs to a family of guanyl-nucleotide-binding proteins coupled to meatbotropic receptors that, when activated bind to other proteins

a chemical that carries a message to initiate a biochemical process
activated by a NT

is an increase in the number of receptors

is a decrease in the number of receptors

diffusion away from synaptic cleft
degradation by enzymes in the synaptic cleft
reuptake into the presynaptic neuron for subsequent re-use
taken up by neighboring glial cells
*not mutually exclusive

excitatory
typically located on dendrites
round vesicles
dense material on membranes
wide cleft
large active zone

inhibitory
typically located on cell body
flat vesicles
sparse material on membranes
narrow cleft
small active zone

the chemical must be synthesized in the neuron or otherwise be present in it
when the neuron is active the chemical must be released and produce a response in a target
the same responses must be obtained when the chemical is experimentally placed on the target
a mechanism must exist for removing the chemical from its site of action after its work is done

class of quick acting NT
synthesized from dietary nutrients and packaged ready for use in axon terminals
ex.: ACh, DA, NE,EP, Glu, GABA, Gly, histamine

rate-limiting factory
_ restricts the rate at which all the catecholamines can by synthesized

glutamate-main excitatory transmitter
GABA-main inhibitory transmitter

main excitatory transmitter
cannot pass blood-brain barrier–synthesized within the cell using glutamine released by glial cells, glial cells take up released glutamate and transform to glutamine

a multifunctional chain of amino acids that act as a NT
synthesized from mRNA on instructions from the cell’s DNA
do not bind to ion channels; do not have direct effects on the voltage of the postsynaptic membrane, act indirectly via G-protein coupled receptors

synthesized in cell as needed
easily crosses cell membrane
support metabolic processes

pathway that coordinates activity through a single NT

cholinergic

neuron that uses ACh as its main NT
excites skeletal muscles to cause contractions
ACh produced in nuclei in midbrain and basal forebrain

cholinergic neurons from the CNS control both divisions
both NE and ACh have excitatory effects on some organs and inhibitory effects on others

cholinergic
dopaminergic x2
noradrenergic
serotonergic
cell bodies are located in a nucleus in the brainstem and their axons are distributed through a wide region of the brain

involved in attention, memory
maintaining neuronal excitability–helps maintain working electroencephalographic pattern
Alzheimer’s disease–linked to decreased ACh synthesis, treated with acetylcholinesterase inhibitors

mesostriatal–originates in substantia nigra, projects to striatum, maintaining normal motor behavior
parkinson’s disease treated with L-dopa
mesolimbocortial–originates in ventral tegmentum, projects to nucleus accumbens, basal forebrain, frontal cortex, reward, motivation, addiction
increased DA= schizophrenia
decreased DA= ADHD, treat with DA stimulants

originates in locus coeruleus, projects throughout cortex
emotion
decreased NE= major depression
increased NE= mania

originate in raphe nuclei, project throughout brain
maintaining wakefulness
learning
increased 5-HT= OCD
decreased 5-HT= depression
abnormalities in brainstem 5-HT neurons linked to sleep apnea and SIDS

endothelial cells of the brain capillaries are surrounded by the end feet of astrocytes attached to the capillary wall, covering about 80% of it
glial cells provide a route for the exchange of food and waste between capillaries and the brain’s extracellular fluid

substance that enhances the effectiveness of a NT

substance that blocks/decreases the effectiveness of a NT

drugs can alter chemical processes at any of the seven major stages of synaptic transmission–synthesis, storage, release, receptor interaction, inactivation, reuptake, degradation

bind to receptor and initiates opposite effect of usual transmitter

bind to the same part of receptor molecule as endogenous ligand

bind to modulatory sites that are not part of the receptor complex that normally binds the transmitter

is that ability of a bound ligand to activate the receptor
partial agonists produce a medium response regardless of dose

is a graph of the relationship between drug doses and the effects
the does ate which the drug shows half of its maximal effect is the _
a drug that has comparable effects at lower doses is more potent

is the separation between the effective does and a toxic one
drugs with wider _ are safer

decrease in response to a drug with the passage of time

organ systems become more effective at eliminating the drug, increase in number of enzymes used to break down substance

target tissues show altered sensitivity to the drug
activities of brain cells adjust to minimize effects of the substance

response to a novel drug is reduced because of tolerance developed in response to a related drug
suggests that the two drugs affect a common nervous system target

or tranquilizers are depressants–drugs that reduce nervous system activity
GABA
benzodiaxepines–antianxiety agents
barbiturates–produce sedation and sleep, also general anesthesia, coma, death
dissociate anesthetics–group of sedative-hypnotics developed as anesthetics, produce altered states and hallucinations (GHB, ketamine, date rape drugs)
alcohol–similar neurochemical effects as barbiturates, GABAa receptors and increases inhibitory effect, also stimulates dopamine pathways causing euphoric effects, chronic use causes liver damage and thiamine deficiency

first generation–major tranquilizer, drug that blocks D2 dopamine receptor, reduce the positive symptoms of schizophrenia, produce symptoms of parkinson’s disease
second generation-weakly block D2 receptors but also block serotonin 5-HT2 receptors, reduce negative symptoms, affect motivation and reduce agitation but may result in weight gain

proposal that schizophrenia symptoms are due to excess activity of the NT _
evidence–antipsychotic drugs block D2 receptors, amphetamine promotes release of _ and can produce symptoms similar to schizophrenia

MAO inhibitors–block the enzyme MAO from degrading NT such as dopamine, NE, and 5-HT
tricyclic _–first generation _ with a chemical structure characterized by 3 rings that block 5-HT reuptake transporter proteins
second-generation _–action is similar to first generation but is more selective, SSRIs, block the reuptake of serotonin into the presynaptic terminal

used to treat bipolar disorder
mutes the intensity of one pole of the disorder thus making the other pole less likely to recur
mechanism is not well understood–lithium may increase serotonin release, valproate may stimulate GABA activity

compound that binds to a group of brain receptors also sensitive to morphine
2 natural sources– opium used for thousands of years to produce euphoria, analgesia, sleep, and relief from diarrhea and coughing, the brain–peptides in the body that have opioid like effects are collectively called endorphins

peptide hormone that acts on a NT and may be associated with feelings of pain or pleasure
3 classes–endomorphins, enkephalins, dynorphins

drugs with sleep-inducing and pain-relieving properties
codeine
morphine
some synthetic _ prescribed for clinical use in pain management are hydromorphone, levorphanol, methadone
competitive inhibitors can be used to treat opioid addiction after the person has recovered from withdrawal symptoms–nalorphine and nalozone
_ ingestion produces relaxation, sleep, euphoria, constipation, respiratory depression, decreased blood pressure, pupil constriction, hypothermia

an opiate drug synthesized from morphine
more fat soluble and penetrates the BBB faster than morphine, therefore produces very rapid pain relief

behavioral stimulants affect motor activity and mood
psychedelic and hallucinogenic stimulants affect perception and produce hallucinations
general stimulants mainly affect mood

increase motor behavior and elevate a person’s mood and level of alertness
rapid administration of _ is most likely to be associated with addiction

obtained from the leaves of the coca plant
blocks dopamin reuptake
powder is snorted or injected
derivates such as novocaine are used as local anesthetics–reduce cell’s permeability to Na+ thereby reducing nerve conduction

dopamine agonist–blocks dopamine reuptake transporter, leaving more dopamine available at the synaptic cleft, stimulates release of dopamine from presynaptic membrane
both mechanisms increase the amount of DA available in synapses to stimulate DA receptors
some uses–initially an asthma treatment, study aid, improvement of alertness and productivity, weight-loss aid

relatively inexpensive, yet potentially devastating
neurotoxic–causes brain damage with prolonged use, damages both DA and 5HT neurons

drugs that cause a general increase in the metabolic activity of cells
caffeine–inhibits the enzyme that normally breaks down the second messenger cyclic AMP, increase in cAMP leads to an increase in glucose production within cells, which makes more energy available and allows for higher rates of cellular activity, blocks the effect of adenosine an endogenous neuromodulator that normally inhibits catecholamine release

alter sensory perception and cognitive processes and can produce hallucinations
ACh- atropine, nicotine
NE- mescaline
HT5- LSD, psilocybin, ecstacy
Anandimide- THC
Glutamate- PCP, ketamine

LSD, mescaline, magic muschrooms have visual effects
have diverse neural action including those on NE, HT5, ACh and opiate systems
many have potential clinical uses for treatment of mental health disorders–OCD, anxiety, depression, PTSD

either block or facilitate transmission of ACh synapses
nicotine–increases heart rate, blood pressure, hydrocholiric acid secretion, and bowel activity, acts as an agonist on nicotinic ACh receptors in the body and brain, rewarding effects are mediated by receptors in ventral tegmnetal area

mescaline produces pronounced psychic alterations, including a sense of spatial boundlessness and visual hallucinations

LSD and psilocybin stimulate some HT5 receptors
ecstasy elevates _ concentrations by blocking reuptake and stimulating release
chronic use can cause depression, memory disturbances and alters the structure and function of _ neurons

homologs of marijuanna produced in the brain–acts as retrograde messengers and may influence NT release from the presynaptic neuron

alters memory formation, stimulates appetite, reduces pain sensitivity, protects from excitotoxic brain damage, lowers blood pressure, combats nausea, lowers eye pressure from glaucoma
2 cannabinoid receptors (metabotropic)– CB1 only in the CNS, CB2 prominent in the immune system

PCP and ketamine can produce hallucinations and out of body experiences
they exert part of their action by blocking glutamate NMDA receptors involved in learning
many _ like substances kill neurons–influx of Ca2+ into the cell which through second messengers activates a suicide gene leading to apoptosis