Neurotransmitters Flashcards
Acetylcholine
Excitation
Found in the CNS in two regions:
1. pontomesencephalic region (widespread cortex)
2. nuclear groups of the BF (widespread cortical regions)
Attention, memory/ learning, and higher cognitive functions.
Two subclasses:
1. Muscarinic –> mediate the main cog. effects attributed to cholinergic pathwatys (e.g., attention, memory, STM)
2. Nicotinic –> rapid neural and neuromusclar transmission within the sympathetic & parasympathetic pathway).
Drugs with strong anticholinergic properties (e.g., antihistamines, first- generation antipsychotics, and tricyclic antidepressants) may exert negative effects on these areas, particularly when administered to the elderly or others with reduced cognitive and or cerebral reserve.
Norepinephrine (Noradrenaline: stress hormone)
Excitation
Arousal, shifting attention, mood, sleep-wake cycle
Plays role in depression, bipolar disorder, anxiety/OCD
Areas:
1. locus coerulus
2. Lateral tegmental area of pons & medulla.
Drugs commonly prescribed for ADHD (methylphenidate [Ritalin, Concerta], amphetamine/dextroamphetamine [Adderall]) increase levels of NE and dopamine,
Atomoxetine (Strattera) is a specific norepinephrine reuptake inhibitor that only affects NE.
Serotonin
Inhibition
Location: Raphe Nuclei of midbrain, pons, & medulla.
1. Rostral –> thalamus, cortex, BG
2. Dorsal –> cerebellum, medulla, spinal cord
Mood, arousal, pain, temperature NOT ATTENTION
Psychiatric syndromes: Anxiety,OCD, depression, aggressive behavior, eating disorders
Drugs affecting serotonin metabolism are commonly prescribed for depression, generalized anxiety, and social phobia. Some (e.g., fluoxetine [Prozac], sertraline [Zoloft]) are serotonin-specific reuptake inhibitors
Others (e.g., venlafaxine [Effexor]) effect reuptake inhibition in the serotonergic and noradrenergic system.
Drugs may be used in combination w/ serotonin 2A antagonists (e.g., trazodone [Desyrel], mistrazapine [Remeron], others) to treat refractory depression.
Dopamine
Inhibitory and excitatory
Exist primarily in the substantia nigra pars compacta (SNpc) and VTA.
Three Subsystems:
1) Mesostriatal system- –> arises from SNpc and projects to the striatum (caudate, putamen) in BG. (Meso= middle brain/midbrain, striatal = striatum; input from BG)
* pathway implicated in Parkinson’s disease, and dysfunction here can produce disabling motor and nonmotor symptoms
2) Mesolimbic pathway –> arises in VTA and projects to the medial temporal lobe, amygdala, cingulate cortex
* key role in reward functioning and has been implicated in addictive behavior.
* overactivity = positive symptoms of schizophrenia (e.g., delusions, hallucinations) that respond well to dopamine-serotonin 2A antagonist drugs. Include: clozapine [Clozaril], quetiapine [Seroquel], risperidone [Risperdal].
3) Mesocortical system –> Arises from the VTA and projects primarily to cortical regions of the frontal lobe.
* key role in EF, working memory, top-down attention, and initiation of motor activity.
* Dysfunction = negative symptoms of schizophrenia, as well as dysexecutive syndrome and bradykinesia.
Gamma-aminobutyric acid (GABA)
Inhibitory
Location: reticular nuclues of the thalamus (e.g., critical for gating thalamocortical interactions)
(Broad functions) regulating sleep and arousal, attentional shifting beytween response-reinforcement contigencies.
Key basis for neuromodulation.
Many anti-anxiety drugs act to ENHANCE GABA-ergic neurotransmission, offsetting abnormally excitatory influences.
Huntington’s
Glutamate
Excitation
Most abundant NT in the brain.
(Broad functions) learning and memory, particularly long-term potentiation (LTP), and synpatic plasticity/neurogensis (e.g., development to new experience dependent memories).
Adrenergic (epinephrine) neurons originate in what area?
(lateral) tegmental area
Which three neurotransmitters are involved in depressive disorders?
Dopamine, serotonin, and norepinephrine
Benzodiazepines can affect memory and psychomotor speed by:
potentiating GABA-ergic transmission, by exerting their sedative and antianxiety properties
Site of production for: serotonin, dopamine, adreneric/epinephrine, acetylcholine
serotonin - raphe nuclei (brainstem)
dopamine - substantia nigra & lateral tegmental area
Adrenaline (epinephrine) - Locus coeruleus (within the pons) & adrenal medulla (small organ on top of kidney)
acetylcholine - basal forebrain
Examples of catecholamines
Dopamine (increased with stimulant meds)
Norepinephrine (increased with non-stimulant meds)
How does NMDA receptor antagonist enhance cognition?
Selectively inhibiting pathological aspects of glutamatergic activation while preserving the physiological activation of NMDA receptors, thus restoring LTP.
Which NMDA receptor antagonist is widely used in AD?
Mematine (Namenda)
