Term
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Definition
-malfunctions in neurodevelopment and neurodegenerative changes
-changes in anatomy and behavior
-NTs-DA,5-HT,glutamate and ACh (we do not know if they are cause or result) |
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Term
| neurodegenerative changes most apparent and chaotic at age |
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Definition
| 20-40 (apoptosis/necrosis) |
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Term
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Definition
-caused by excess DA in specific neural tracts (areas high in D2 receptors)
-support-most antipsychotics block D2 receptor
-the better the drug is at blocking D2 the lower the dose
-DA agonists and amphetamines exacerbate it and cause hallucinations
-increased DA receptor number in untreated
-BUT newer drugs have low affinity for the D2 receptor |
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Term
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Definition
-conc. where 50% of receptors are inhibited (affinity)
-as IC50 increases, dose increases |
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Term
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Definition
-thinking and mood (mesocortical/mesolimbic)
-extrapyramidal function (nigrostriatal)
-prolactin release (tuberoinfundibular)
-emesis (CTZ trigger zone) |
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Term
| D2 (Gi coupled) highly expressed in |
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Definition
-cortex (arousal/mood)
-limbic system (emotion)
-striatum (motor control)
-ventral hypothalamus/anterior pituitary (dec. prolactin secretion)
-blocking DA will block all of these effects and cause adverse effects of antipsychotics |
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Term
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Definition
-dec. DA in mesolimbic (positive symptoms)
-inc. DA in mesocortical (negative and cognitive symptoms)
-leave nigrostriatal alone |
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Term
| what causes the decrease in DA in mesocortical pathway |
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Definition
-not sure
-DA neurons not producing/releasing enough DA
-D2 receptors are blocked by antipsychotic agents
-too much 5-HT activity leads to dec. DA release (goal of tx, dec 5-HT in mesocortical pathway) |
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Term
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Definition
-blood concentration of 5-HT is higher
-results in DEC. DA ACTIVITY IN THE MESOCORTICAL PATHWAY
-serotonin binds to 5HT2A on glutamatergic neurons which accelerates DA activity in the frontal cortex
-leads to ENHANCEMENT OF MESOLIMBIC PATHWAY (POSITIVE SYMPTOMS) |
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Term
| serotonin receptor 2 (ABC) |
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Definition
-CNS, PNS, smooth muscle, platelets
-BEHAVIORAL EFFECTS, smooth muscle contraction, platelet aggregation |
|
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Term
| all serotonin receptors are GPCR except |
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Definition
| 5-HT3 (sodium potassium channels) |
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Term
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Definition
-widespread projection originate in raphe nucleus
-MANY ROLES:
-PSYCHOTIC BEHAVIOR (LSD and MDMA play a role in altering 5-HT)
-sleep, depression, OCD, appetite, pain perception, vomiting |
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Term
| pure 5-HT antagoists efficacious? |
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Definition
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Term
| why less EPS with drugs that also block 5-HT2A receptors |
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Definition
| -5-HT normally inhibits the nigrostriatal cicuit |
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Term
| normal DA 5-HT nigrostriatal pathway |
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Definition
| -DA is released because 5-HT is not binding to 5-HT2A receptor (inhibiting movement) |
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Term
| antipsychotic binding to D2 |
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Definition
-antipsychotic binds only to D2 receptor
-5-HT binds to 5-HT2A receptor (dec. DA release)
-movement disorders result |
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Term
| antipsychotic binding to D2 and 5-HT2A receptors |
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Definition
-a5-HT cannot bing (inc. DA)
-DA competes with antipsychotic for D2 receptor
-movement is not inhibited |
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Term
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Definition
-HYPOfunctional system leads to schizo
-LACK of glutamate leads to changes in DA activity associated with schizo
-PCP (NMDA antagonist) mimics schizo
-changes in expression of NMDA receptors and their associated proteins in schizo |
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Term
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Definition
-ionotropic (NMDA, AMPA,kainate)
-metabotropic (mGluR1-8) |
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Term
| lack of glutamatergic activity leads to |
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Definition
| -increase and decrease in DA activity in key areas of the brain |
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Term
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Definition
-deficits in M1 and M2 receptors and ChAT activity in schizo pts
-M receptors play a role in excitability, learning, and memory
-many have defect in nACh receptors (alpha4, beta2, and alpha7)
-nicotine in attention in smokers
-agonists at nicotinic receptors may be effective in treating the cognitive and amerliorate side effects |
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Term
| is high incidence of smoking in schizo pts a result of an effort to self medicate |
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Definition
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