Presentation on theme: "Dopamine Theory of Schizophrenia"— Presentation transcript:
1 Dopamine Theory of Schizophrenia Schizophrenia is caused by too much dopamine (DA)DA antagonists are effective neuroleptics (antischizoprenic drugs)ChlorpromazineReserpineEvidenceNeuroleptics take 2-3 weeks to workParkinson’s disease (PD) side effectsPD = reduced DA in striatumSchizophrenia = too much DACocaine/amphetamine increase DA levels and induce schizophrenia type symptoms (stereotype behavior)
2 Problems with DA Theory Different drug mechanismsReserpine depletes DABy breaking down synaptic vesiclesChlorpromazine does not deplete DADA levels are normalIncreased levels of DA metabolitesIs a receptor blocker
5 Revised DA TheoryIncreased DA receptor activation, rather than DA levels per seExplains both clorpromazine and reserpineOther drugs reveal a positive relationship betweenaffinity to bind to DA receptorsand antischizophrenic potencyHowever…
6 Revised DA Theory - D2 receptors Some drugs such as haloperidolAre potent neurolepticsBut initially showed low affinity for DA receptorsHowever…There are 5 subtypes of DA receptorsHaloperidol is a D2 receptor antagonistThe relationship between receptor affinity and neuroleptic potency is better for D2 receptors
8 D2 receptor theory Is not a perfect explanation 30% of patients do not respond to D2 receptor antagonistsAtypical neuroleptics such as clozapine bind D1, D4 and several 5-HT receptors (low affinity for D2)Neuroanatomical findingsWidespread brain damage…not evenly distributed (prefrontal, cingulate and hippocampal areas are smaller than normal)Evidence of a developmental abnormality
9 D2 receptor theory Qualifications offered: Why do neuroleptics take 2-3 weeks to workInitial increase in DA releaseDecreased release after 2-3 weeksA retrograde signal to increase DA release is inhibited over timei.e., the dopamine-cell depolarization blockThe schizophrenias (multiple subtypes)Positive symptoms and negative symptomsD2 antagonists more effective in reducing positive symptomsImproved diagnosis is needed to generate a better theory and more effective treatments
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