Animal Models Of Schizophrenia Flashcards
What is an animal model?
An animal model is a simplified model of a clinical condition, designed to examine the constructs of a clinical condition and test effectiveness of treatments.
What is schizophrenia?
Schizophrenia is a form of psychosis characterised positive, negative and cognitive symptoms. E.g. Abnormal ideas (delusions), formal thought disorder (thought derailment, loss of goals), cognitive dysfunction (deficits in executive function, verbal and visual memory)
What validities should be considered with an animal model?
Predictive validity: effective theraputically
Construct validity: constructs similar to real condition
Face validity: does model look like real condition
What is the dopamine hypothesis of schizophrenia?
Believes that schizophrenia is caused by an excess of dopamine especially in the mesolimbic system (ventral tegmental area to the nucleus accumbens). Examined through dopamine antagonists and amphetamine. Only accounts for positive symptoms.
What did Grey et al (1997)?
Grey et al (1997) found that if you destroyed the nucleus accumbens latent inhibition was potentiated.
Similarly intra-accumbens haloperidol (typical antipsychotic - dopamine antagonist) reversed the blockade caused by amphetamine (increases extracelluar dopamine)
Who showed effects of dopamine in social interaction?
Samms-Dodd (1998) dopamine has a role in social interaction (decreased in schizoohrenics) antipsychotic successfully reversed effects of amphetamine at levels which also affected saline vehicle.
What is the glutamate hypothesis for schziophrenia?
Decrease in Glutamate activity, mainly studied through glutamate antagonists and ketamine. Explains positive, negative and cognitive symptoms
How has ketamine been used in studies?
Sub chronic application of ketamine has been applied in a rat model (nmda, subtype of glutamate, antagonist) decreases non-aggressive behaviour (schizophrenic type) reversed by diazepam but no effect on controls (Becker and greckson, 2004)
How has phencyclidine been used in rat studies?
Sub chronic phencyclidine (glutamate antagonist, dissociative anaesthetic) disrupts NOR (deficits in visual memory) reversed by clozapine (Grayson, Ian’s, Neil’s, 2007)
What is the evidence for the combination approach of schizophrenia (glutamate and dopamine)?
Sub chronic application of ketamine induces neuronal changes in behaviour and parameters of dopaminergic, glutamatergic and serotenergic neuro transmitters. 1st treatment reduced activity time, 4th no effect (tolerance), 4th week disrupted LI. Increased dopamine binding in frontal cortex, and increase in serotonin binding in striatum, hippocampus and frontal cortex (Becker et al, 2003)
What makes an animal model novel?
Used to be thought that schizophrenia was social or psychological but animal models have since change this view (Lipska and Wierenga, 2004). Heuristic models need to show neural changes that were not directly manipulated by the animal model.
Intracerebralenthallic injections of kanic acid in neonatal rats - reduction in neural numbers in the dorsal hippocampus and changes in glutamate expression in glutamate expression (Montgomery et al 1999)
Recent research in schizophrenic research?
Dimer et al (2014) found that olanzapine (which normally induces cardiometabolic disorders such as diabetes) if packaged into biodegradable polymeric lipid-core nanocapsules, extends effect and reduces side effects
