lecture 22 LOs Flashcards
behavioural assay to model neg symptoms of schizophrenia
social interaction mesaures, deficit in grooming, measures of motivation (progressive ratio responding, choosing between rewards of different costs/benefits)
behavioural assay to model cog symptoms of schizophrenia
numerous tasks have been developed that resemble those used in humans to measure deficits in different domains of cog affect in schizophrenia
behavioural assays to model positive symptoms of schizophrenia
sensitivity to amephtamine/PCP: most animal models induced enhanced response to these drugs
prepulse inhibition (PPI) of acoustic startle: people w schizophrenia have difficulty filtering and report being overwhelmed by sensory stimuli
*loud sound will startle a rat
*quieter sound (prepulse) right before the loud sound will normally reduce the startle response
*PPI deficits are present in schizophrenic patients (and in many animal models)
*reversal of induced sensory-filtering deficits predicts antipsychotic effects
what are antipsychotic (aka neuroleptic) drugs effective at treating
positive symptoms (delusions and often hallucinations)
ineffective at treating neg/cog symptoms
what do all antipsychotics block to some degree
D2 receptors
D1 antagonists have no effect or worsen symptoms
many can bind to other receptors but there is no clear relation between effectiveness and binding to other targets
what does acute treatment with antipsychotics do
reduces hyperactive symptoms relatively quickly, but full effects take about 2 weeks to emerge
what does chronic D2 blockades lead to
actions on autoreceptors that cause longer lasting change in DA synthesis, release, and metabolism
what eventually happens to drug induced increase in DA neuron firing
reduces their activity like a depolarization block
what is the parkinsonism side effect of antipsychotic drugs
motor side effects (primarily mediated by the DA pathway)
what antipsychotic drugs tend to have fewer motor side effects
ones with anti-cholinergic action
what is tardive dyskinesia (TD)
side effect from antipsychotic drugs
stereotyped involuntary movements, particularly of the mouth/jaw, quick and uncontrolled movements of the arms and legs
symptoms can persist after the treatment is discontinued
chance of TD increases w length of treatment
what are four other side effects of antipsychotic drugs
neuroendocrine: decreased sex drive, disrupted menstrual cycle, inhibition of growth hormone release, increased prolactin (can cause lactation in men) all mediated by D2 antagonism
weight gain/body temp irregularities: mediated by actions on serotonin receptors
anticholinergic: dry mouth, blurred vision, difficult urination, GI issues
antiadrenergic: dizziness, faintness, blacking out
what do atypical/second generation drugs do
reduce psychosis as effectively as classical drugs, but produce fewer extra-pyramidal effects
some newer drugs don’t induce TD or increase prolactin
what do broad spectrum antipsychotics do
atypical antipsychotic
block other receptors as well as D2
what does clozapine do
atypical antipsychotic
has weaker affinties for D2 and strong affinities for serotonin, ACh, hisamine
can be more effective for those who do not respond to typical neuroleptics
