Psyc4130 1nd Edition Lecture 32 Outline of Last Lecture I. SchizophreniaII. HallucinationIII. Cognitive SymptomsIV. EtiologyV. Etiology FactorsVI. Brain Abnormalities Outline of Current Lecture I. Evidence for DA HypothesisII. Classic AntipsychoticsIII. D2 Antags Are Not Well-ToleratedIV. The DA Hypothesis SequelV. The PFC modulates Activity in the VTAVI. Atypical AntipsychoticsVII. NMDA AgonistsCurrent 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 antagonistso 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 sideso ParkinsonismThese 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 Parkinsonismo Supersensitivityo Protrusions of the tongue, flailing of limbso 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 stimulationo 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 & Amygo 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-PFCo 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
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