BIOL 4220 Lecture Notes - Lecture 7: Medial Forebrain Bundle, Tricyclic Antidepressant, Biogenic Amine
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Cell$origin$=>$Rape$nucleus$
MFG$=>$medial$forebrain$bundle$
PAG$=>$periaquaductal$gray$($in$brainstem)$
• Gating$pain$
$$
Projection$$
• Parallel$w/$NE$system$
• But$not$as$widespread$or$diffused$
• Action$is$“opposite”$of$NE$
• Calming$effect$vs.$stimulant$effect$
• Sense$of$security$and$safety$
$$
• Sexual$behavior$regulation$in$the$Raphe$Nuc$in$male$
• Sexual$behavior$regulation$more$in$hypothalamus$$
$$
Depression$
• Biogenic$amine$hypothesis$
• Hypofunction$of$5-HT$
• Anti-depressant$targeting$5-HT$system$
◦ SSRI$=>$selective$serotonin$reuptake$inhibitory$
◦ MAOI$=>$momoamine$oxidase$inhibitor$
◦ TCA$=>$tricyclic$antidepressant$
◦ Dual-action$antidepressant$
• Action$on$5-HT$but$also$NE$or$DA$
◦ Requires$4-6$week$for$therapeutic$effects$to$kick$in$
• DNA$expression$
• Newer$antidepresant$
◦ Fast$acting$antidepressant$
◦ PCP,$ketamine$(sub-anesthetic$dose)$
◦ Lift$depressant$instant$within$4$hr$of$injection$
• Last$for$1$month$
◦ Instantly$increase$dendrite$spines$density$
• Strengthen$synaptic$connection$instantly$
◦ Byproduct$of$breaking$down$PCP,$Ketamine$=>$active$ingredient$=>$
Lift$depression$
◦ Prodrug$=>$no$action$by$itself$=>$but$once$inside$the$system$=>$
metabolize$it$=>$endproduct$is$the$active$ingredient$
5-HT$system$
• Promote$well$being$of$animals$
• Promote$mood$state$that$is$calming$and$safe$
• Infants$dependent$on$maternal$care$
• Releasing$5-HT$in$both$mother$and$infant$=>$bond$=>$sense$of$secure$and$
safety$
• Separation$anxiety$if$mother$is$not$around$to$comfort$you$
• Lose$the$sense$of$security$and$safety$
• Lead$to$anxiety$(GAD)$generalized$anxiety$disorder$
• Treat$cause$of$anxiety$
◦ Target$5-HT$system$
◦ Buspar$
◦ Sense$of$safety$and$security$
◦ Anxiety$becomes$non-issue$
• Treatment$for$anxiety$
◦ Treat$symptom$
◦ Valium,$Xanax$
◦ Inhibit$amygdala$
◦ Suppress$fear$
• MDMA$(methylenedixoxymethamphetamine)$
◦ Ecstasy,$molly,$x,$rolling$
◦ Induced$Cytoplasmic$release$of$5-HT$
• Flush$out$vesicular$content$of$5-HT$into$cyto$then$into$synapse$
• Activate$post-synaptic$
◦ Initially$patented$by$Merck$(1900)$
• Diet$pill$
• Appetite$suppressor$
◦ Military$test$for$drug$for$interrogation$
• Truth$serum$
• Honest$
• Cannot$lie$
• Tell$truth$
• But$military$missed$the$effects$