Chapter 4 Flashcards
neurotransmitter
chemical released from the presynaptic axon terminal that serves as the basis of communication between neurons
- qualifications:
+ substance exists in presynaptic axon terminals
+ is synthesized in presynaptic cells
+ is released when action potentials reach axon terminals
+ receptors for the substance exist on postsynaptic membrane
+ when applied, substance produces changes in postsynaptic cells
+ blocking substance release prevents changes in postsynaptic cell
types of receptors
- ionotropic: fast; open an ion channel when the transmitter molecule binds; fast onset + decay (millisecond)
- metabotropic: slow; alter chemical reactions in the cell (e.g. G protein system) to open an ion channel; slower onset, long response and duration (second or minute)
ligand
substance that fit receptors exactly and activates or blocks them
- categories:
+ endogenous: produced inside the body (e.g. neurotransmitters and hormones)
+ exogenous: produced outside of body (e.g. drugs and toxins)
types of ligands
- agonist: initiates or activates the normal effects of the receptor
- antagonist: blocks the receptor from being activated by other ligands
- inverse agonist: initiates an effect that is the opposite of the normal function
drugs as exogenous ligands
- if act as agonists, antagonists or inverse agonists: COMPETITIVE ligands - bind to the same part of receptor molecule as endogenous ligands
- NONCOMPETITIVE ligands (also called neuromodulators): bind to modulatory sites that are not part of the receptor complex that normally binds the transmitter
types of neurotransmitters
- amine: acetylcholine, dopamine, norepinephrine, adrenaline, serotonin
- amino acid: GABA, glutamate
- peptide
- gas: nitric oxide, carbon dioxide
acetylcholine (ACh)
mapped by enzymes involved in synthesis; stored in cholinergic nerve cell bodies and projections
+ roles: signaling muscle movement, sensation of pain, learning + memory formation, regulation of endocrine system, sleep
dopamine (DA)
- found in substantia nigra of the mesostriatial pathway (in midbrain)
- role: motor control (neuronal loss in pathway leads to Parkinson’s disease) - found in ventral tegmental area (VTA) of the mesolimbocortical DA pathway (in midbrain)
- role: reward, reinforcement, and learning (abnormalities lead to schizophrenia & neurodegenerative diseases)
norepinephrine (NE)
also called noradrenaline
released in 3 brainstem regions: locus coeruleus (pons), lateral tegmental system (midbrain), and dorsal medullary group
- role: modulate processes of mood, arousal, and sexual behavior
serotonin (5-HT)
found in raphe nuclei
- role: sleep, mood, sexual behavior, anxiety
amino acid transmitters
- GABA: inhibitory - trigger IPSP
- glutamate: excitatory - trigger EPSP
+ excitotoxicity: neural injury such as stroke may cause excess release of glutamate, which is toxic to neurons
peptide
2+ amino acids linked in a chain; act as neurotransmitters or hormones
- opioid peptides: mimic opiate drugs (e.g. morphine)
- peptides in gut, spinal cord, or brain
- pituitary hormones
nitric oxide (NO)
produced in dendrites, diffuses as soon as it is produced into target cell and stimulates production of second messengers
mechanism of drugs
affect synaptic transmissions: either act on presynaptic terminals or postsynaptic membrane
- e.g. local anesthetics block sodium channels and therefore block action potentials in pain fibers
agonist vs. antagonist drugs
- agonist: initiates or activates normal effects of receptor
+ e.g. dopamine, morphine, nicotine - antagonist: blocks receptor from being activated by other ligands
+ e.g. haloperidol (treatment of schizophrenia)
affinity
or binding affinity
degree of chemical attraction between a ligand and receptor
- high level: drug will bind with matching receptor even at low doses and stay for a relatively long time
- low level: drugs bind fewer receptor molecules
efficacy
or intrinsic activity
ability of a bound ligand to activate the receptor
- agonists -> high efficacy, antagonists -> low
dose-response curve (DRC)
graph of the relationship between drug doses and the effects (effects - y axis, dose - x axis)
- effective dose 50% (ED50): dose at which the drug shows half of its maximal effect
- comparable effects at lower doses -> more potent
tolerance
condition in which an individual becomes less responsive to a drug after repeated exposure (continued use)
- mechanism: body = regulatory feedback system to protect against unbalanced brain chemistry -> adapts to presence of drugs to offset effects -> develops tolerance
- as tolerance develops, more of the drug is needed to produce the same effect
types of tolerance
- metabolic: organ systems become more effective at eliminatingw/cleaning the drug (e.g. liver) before it has a chance to affect the brain
- functional: target tissue may decrease sensitivity to drug as a result of change in # of receptors present in cell membrane
+ down regulate: decrease # of receptors - response to agonists
+ up regulate: increase # of receptors - response to antagonists
withdrawal symptoms
unpleasant sensations that occur when one stops using a drug
- can be psychological (e.g. anxiety, irritability, depression, etc.) or physical (e.g. tremors, nausea, sweating, etc.)
- prolonged + repeated use of drugs change the way nerve receptors work in the brain and make them dependent upon the drug to function
- recreational drugs trigger dopamine release in reward system -> addictive
drug effects on presynaptic mechanisms
- affect transmitter synthesis enzymes
- affect storage in vesicles
- postsynaptic receptors can be blocked or activated by drugs
drugs as presynaptic control
affect transmitter reuptake (how long transmitters remain in synapse) and interfere with transporters (specialized proteins that return transmitter to the presynaptic membrane)
- cocaine: alleviates hunger, promotes endurance, enhances sense of well-being; blocks monoamine transporters (especially dopamine) and slows reuptake
- caffeine: blocks adenosine and stimulates catecholamine (e.g. dopamine) release -> causes arousal
drugs as postsynaptic control
- nicotine: increases heart rate, blood pressure, hydrochloric acid secretion, and bowel activity; acts as agonists on nicotinic ACh receptors in body & brain
- alcohol: biphasic effects - stimulant phase followed by depressant phase; activate GABA receptors and increases inhibitory effects; stimulates dopamine pathways; induces social disinhibition, loss of motor coordination, and feeling of euphoria
+ chronic use seriously affects frontal lobes & shrinks cortex + kills neurons
+ periodic overconsumption (bingeing) may cause brain damage and reduce neurogenesis - marijuana: causes relaxation, mood alteration, stimulation, hallucination, and paranoia
drug abuse
reason: drugs cause strong feeling of euphoria or reward via dopamine release in nucleus accumbens
- drugs stimulate reward pathway in VTA
models of drug abuse
- physical dependence model:
+ also called withdrawal avoidance model
+ theory: abusers use drugs to avoid withdrawal symptoms (negative reinforcement)
+ BUT some addicted patients do not experience strong withdrawal symptoms - positive reward model:
+ theory: drug use is a behavior controlled by positive rewards
+ pleasant sensations and behaviors associated with addictive drugs increase probability of use
+ addictive drugs are positive reinforcers that increase the effect of dopamine receptor in the limbic system
