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1 Dopamine Theory of Schizophrenia Schizophrenia is caused by too much dopamine (DA) DA antagonists are effective neuroleptics (antischizoprenic drugs)

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Presentation on theme: "1 Dopamine Theory of Schizophrenia Schizophrenia is caused by too much dopamine (DA) DA antagonists are effective neuroleptics (antischizoprenic drugs)"— Presentation transcript:

1 1 Dopamine Theory of Schizophrenia Schizophrenia is caused by too much dopamine (DA) DA antagonists are effective neuroleptics (antischizoprenic drugs) DA antagonists are effective neuroleptics (antischizoprenic drugs) –Chlorpromazine –Reserpine Evidence Evidence –Neuroleptics take 2-3 weeks to work –Parkinson’s disease (PD) side effects –PD = reduced DA in striatum –Schizophrenia = too much DA –Cocaine/amphetamine increase DA levels and induce schizophrenia type symptoms (stereotype behavior)

2 2 Problems with DA Theory Different drug mechanisms Reserpine depletes DA Reserpine depletes DA –By breaking down synaptic vesicles Chlorpromazine does not deplete DA Chlorpromazine does not deplete DA –DA levels are normal –Increased levels of DA metabolites –Is a receptor blocker

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5 5 Revised DA Theory Increased DA receptor activation, rather than DA levels per se Explains both clorpromazine and reserpine Explains both clorpromazine and reserpine Other drugs reveal a positive relationship between Other drugs reveal a positive relationship between –affinity to bind to DA receptors –and antischizophrenic potency However…

6 6 Revised DA Theory - D2 receptors Some drugs such as haloperidol Are potent neuroleptics Are potent neuroleptics But initially showed low affinity for DA receptors But initially showed low affinity for DA receptorsHowever… –There are 5 subtypes of DA receptors –Haloperidol is a D2 receptor antagonist –The relationship between receptor affinity and neuroleptic potency is better for D2 receptors

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8 8 D2 receptor theory Is not a perfect explanation 30% of patients do not respond to D2 receptor antagonists 30% of patients do not respond to D2 receptor antagonists Atypical neuroleptics such as clozapine bind D1, D4 and several 5-HT receptors (low affinity for D2) Atypical neuroleptics such as clozapine bind D1, D4 and several 5-HT receptors (low affinity for D2) Neuroanatomical findings Neuroanatomical findings –Widespread brain damage –…not evenly distributed (prefrontal, cingulate and hippocampal areas are smaller than normal) Evidence of a developmental abnormality Evidence of a developmental abnormality

9 9 D2 receptor theory Qualifications offered: Why do neuroleptics take 2-3 weeks to work Why do neuroleptics take 2-3 weeks to work –Initial increase in DA release –Decreased release after 2-3 weeks –A retrograde signal to increase DA release is inhibited over time –i.e., the dopamine-cell depolarization block The schizophrenias (multiple subtypes) The schizophrenias (multiple subtypes) –Positive symptoms and negative symptoms –D2 antagonists more effective in reducing positive symptoms –Improved diagnosis is needed to generate a better theory and more effective treatments


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