CH 7 Flashcards
ACh is a key NT in both ___ and _____. In the _____ it is used in all _____ junctions and in the _______ nervous system. In the CNS, multiple cell body regions enervate _______/_____ regions ACh ____ in the striatum
PNS, CNS, PNS, neuromuscular, parasympathetic, cortical/subcortical, interneurons
a precursor to ACh that is from foods
choline
the other precursor to ACh
acetyl coenzyme A (acetyl CoA)
the enzyme that makes ACh from choline and acetyl CoA; only in ACh neurons
choline acetyltransferase (ChAT)
the rate of ACh synthesis is controlled by the availability of ____ and rate of ____ _____. ChAT works more efficiently when the neuron is firing ______. No selective ____ of ChAT have been found
precursors, neuron firing, a lot, inhibitors
transporters that package ACh into vesicles
vesicular ACh transporters (VAChT)
drug that blocks VAChT, reducing ACh levels
vesamicol
A toxin that causes massive ACh release in the PNS leading muscle pain, tremors, nausea, vomiting, salivation and copious sweating
black widow spider venom
inhibits ACh release selectively in the neuromuscular junction
botulinum toxin
Inhibition of cholinergic activity can be deadly because of ____ _____. ____ can be affected as well. Botox ____ binds to proteins involved in ACh release and prevents release
muscular paralysis, irreversibly
Unlike many transmitters, ACh does not undergo direct ____
reuptake
the enzyme that rapidly breaks down ACh to choline and acetic acid
acetylcholinesterase (AChE)
AChE is located on ______ membranes and also in _____ cells that metabolize ____ ACh. It has a very high _____ for ACh, and breaks it down within _____
postsynaptic, presynaptic, excess, affinity, ms
After ACh breakdown, most choline is taken back into the _____ ______ ____ by a choline transporter
cholinergic nerve terminal
drug that blocks choline transporters, reducing the rate of ACh production
hemicholinium-3 (HC-3)
Blocking _____ (ACh inactivation), increases ____ effects of the transmitter
AChE, postsynaptic
Drug that crosses the BBB and is used to inhibit AChE; offsets some of the cognitive decline associated with AD
physostigmine
ACh neurons die off in the early stages of ____, and multiple other cells die off in late stages
Alzheimer’s disease
Some compounds cause ______ inhibition of AChE, resulting in excess amount of ACh. Weak versions are used as ______. Very toxic varieties such as ____ are used as nerve gasses. ACh ____ and overstimulation of cholinergic synapses throughout the CNS and PNS lead to _____ ____ and death by _____
irreversible, insecticides, serin, accumulation, muscle paralysis, asphyxiation
Nicotinic receptors respond to the agonist ______, and are _____. When ACh binds, the channel allows _____ and ____ flow into the cell and depolarizes it. This type of receptor mediates ______ ____ responses in the CNS and PNS. It consists of ____ subunits (alpha, beta, gamma, sigma, epsilon), with many ____ and ___ of each found in the muscle and brain. Different subtypes can vary in terms of the number of ____ ___ or ____ for ACh, ion flow through channel, ____/____ kinetics, and _____ binding sites. These receptors typically need ____ ACh molecules to open, but the more binding sites, the more the receptor is only active when NT levels are _____.
nicotine, ionotropic, Na+, Ca2+, fast, excitatory, 5, variants, combinations, binding sites, affinity, open/close, allosteric, 2, high
continuous activation of nicotinic receptors initially cause the receptors to be _____, and the channel remains _____ even when an agonist is bound. The channel recovers after a short time with no ______. However, prolonged activation leads to ___ ______, which is persistent, and causes ____ ____ to be lost. This means the cell cannot be excited until the ___ is removed and the membrane ______.
desensitized, closed, stimulation, depolarization block, resting potential, agonist, repolarizes
a drug that causes persistent activation of nicotinic receptors
carbachol
a nicotinic receptor agonist that is a muscle relaxant used in some surgical procedures; it is resistant to breakdown by AChE and causes depolarization block
succinylcholine
a nicotinic receptor antagonist that blocks receptors in both the CNS and autonomic ganglia; used to treat nicotine poisoning
mecamylamine
a nicotinic receptor antagonist that blocks muscle nicotinic receptors but as relatively little effect on central receptors due to its selectively for muscle receptor and low penetrance across the BBB; used as a hunting tool by indigenous peoples; causes paralysis by preventing muscle contracts facilitated by ACh
D-tubocurarine
Other agonists/antagonists that are more _____ for certain types of nicotinic receptors are being developed for certain types of treatment for _____ ____, and ____ ____. These are normally ____ ____ _____
selective, cognitive enhancers, nicotine addiction, positive allosteric modulators
a drug that prevents ACh from affecting DA neurons in the VTA
Chantix
muscarinic receptors respond to ______, and are all ______. There are 5 main subtypes: _____. they operate via second messengers and/or enhance ___ channel opening. Peripheral receptors are found in ______ and ____ muscles in many organs and ______ cells of the pancreas.
muscarine, metabotropic, M1-M5, K+, cardiac, smooth, insulin-producing
M3 receptors are in _____ muscles, and activation results in _______ (e.g. digestive tract). These also mediate other ___ responses such as ___, and _____. Many drugs used to treat psychiatric disorders produces side effects such as _____ ___ due to _____ of peripheral muscarinic receptors
smooth, contraction, secretory, salivation, lacrimation, dry mouth, blocking
____ receptors are cardiac, which ____ heart rate when activated. They also act as presynaptic autoreceptors in the _____.
M2, slows, CNS
a muscarinic receptor agonist which is a parasympathomimetic agent; poisoning leads to exaggerated parasympathetic responses such as salivation, vomiting, diarrhea, urination etc.
pilocarpine
muscarinic receptor antagonists
atropine, scopolamine
muscarinic receptor antagonists can be used ot inhibit _____ effects. They are used to _____ ____, reduce secretions that clog ____, and counteract ______ _____. Central effects include _____, _____, _____, ____ and _____ ____. Higher doses can be toxic, resulting in blurred ____, _____, skin ____, reduced ____, and increased _____ ____
parasympathetic, dilate pupils, airways, cholinergic poisoning, drowsiness, euphoria, amnesia, fatigue, dreamless sleep, vision, psychosis, flushing, secretion, heart rate
Many central actions of ACh are mediated through ____ receptors as well as ____ and ____ receptors.
M1, M3-M5, nicotinic
The striatum contains cholinergic _____. Regulation of ____ depends in part on the balance between ACh and ___. In _____, DA is low and imbalance contributes to _____ symptoms. ______ ______ (muscarinic antagonists) are sometimes prescribed instead of ____ in the early stages.
interneurons, movement, DA, PD, motor, anticholinergic drugs, L-DOPA
ACh cells in the dorsolateral pons project to the the ________ _____ neurons. ACh is ___ on them, and can regulate ___ patterns of firing when something important is happening. This is mediated in part by activation of postsynaptic ___ and _____ receptors, which are also involved in the reinforcing effects of _____ drugs
midbrain DA, excitatory, burst, M5, nicotinic, abused
ACh neurons in the ______ ______ ____ ______ enervate the cortex, hippocampus, and other _____ structures. ACh neurons in this region are ____ with other cells using different transmitters. Selective destruction of cholinergic neurons in this system has revealed that ACh plays a key role in regulating ____ and ___ ___ mediated by forebrain regions, by facilitating _____.
basal forebrain cholinergic system, limbic, intermixed, memory, cognitive functions, attention
When a correct type of lever press gives a rat a food reward, and the rat is given multiple trials in variable intervals
signal detection task
Type of trial where the light comes on very briefly and the rat must press the left lever when levers extend to get the reward
signal trials
When no light is shown and the rat must press the right lever to correctly reject
non signal trials
A _____ study on the signal detection task showed that ACh in the ____ ___ increases in rats performing the task, but not in rats merely pressing the lever for food. When ACh was lesioned in the _______ with ____ _______, performance was impaired, but only with ______, suggesting that the rats were less ______ when the signal was flashed. No effect on correct rejections suggests that impairment was not due to _____ _____
microdialysis, frontal cortex, BFCS, 192 IgG-saporin, hits, attentive, random responding
There are 3 important types of nicotinic receptors: the muscle nicotinic receptor which has ____ binding sites, the neuronal ____/_____ receptor which has 2 binding sites, and the neuronal _____ receptor that has 5 binding sites
2, alpha-4/beta-2, alpha-7
