Psyc4130 1nd Edition Lecture 32 Outline of Last Lecture I Schizophrenia II Hallucination III Cognitive Symptoms IV Etiology V Etiology Factors VI Brain Abnormalities Outline of Current Lecture I Evidence for DA Hypothesis II Classic Antipsychotics III D2 Antags Are Not Well Tolerated IV The DA Hypothesis Sequel V The PFC modulates Activity in the VTA VI Atypical Antipsychotics VII NMDA Agonists Current Lecture Evidence for DA Hypothesis D2 antagonists reduce or eliminate positive symptoms of schizophrenia in about a week In high doses DA agonists e g amphetamines MPH cocaine L Dopa can induce positive symptoms in people with no history of psychosis o Transient and reversible with D2 antagonists o When drugs wear off so do delusions Classic Antipsychotics Major tranquilizers Neuroleptics ALL work by blocking D2 D3 receptors Example Chlorpromazine Thorazine o Educes parkinsons in people who don t have parkinsons D2 Antags Are Not Well Tolerated Acute sides o Parkinsonism These notes represent a detailed interpretation of the professor s lecture GradeBuddy is best used as a supplement to your own notes not as a substitute o Worsen negative symptoms A problem for compliance Tardive dyskinesia o Opposite Parkinsonism o Supersensitivity o Protrusions of the tongue flailing of limbs o Nagrastriatal thing The DA Hypothesis Sequel Recent research has shown that 1 The Sx of SZ do in fact correspond to TOO MUCH mesolimbic activity 2 Neg Sx owe largely to insufficient dopamine and glutamate activity in the PFC o Neg symptoms big problem for therapy under stimulation o Take care of 1 making 2 worse The PFC Modulates Activity in the VTA Top Down Glutamatergic excitatory Stimulates VTA projections back to PFC Inhibits VTA projections to NAc Amyg o Sends feedback to lower levels of brain tells regions to become more or less active Figure 16 12 prefrontal inhibition of dopamine release The PFC Modulated Activity in the VTA Consistent with this hypothesis it s suggested that the eventual emergence of positive symptoms may in fact be part of the sequelae of long term hypofrontality That is to say hypofrontality is primary As a corollary infusion of PCP into the PFC which suppresses activity was shown to increase the release of DA in the NAc Figure 16 11 Chronic PCP Treatment Atypical Antipsychotics Reduce both and Sx Example Aripiprazole Abilify Mechanism of Action PARTIAL AGONIST of DA receptors Decreases activity in mesolimbic system Increases activity in DL PFC o Presence of agonist partial agonist acts as an antagonist NMDA Agonists Glutamate ionotropic receptor Excitatory NMDA itself cannot be used bc it s toxic Glycine and D serine co agonists are being tested May be useful prophylactics during adolescence Figure 16 14 treatment of schizophrenia with NMDA Agonists
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