Carlsson et al (2000)

Question 1

hyperdopaminergia

Answer 1

higher than usual levels of dopamine in the subcortex

Question 2

which two neurochemical explanations for schizophrenia does this study consider

Answer 2

hyperdopaminergia and hypoglutamatergia

Question 3

hypoglutamatergia

Answer 3

low levels of dopamine in the prefrontal cortex

Question 4

Aims

Answer 4

to provide more of an explanation for schizophrenia than simply the dopamine hypothesis

to produce new anti-psychotic drugs that could be more effective with fewer side effects

to consider the need for further research into drug treatments targeting neurotransmitters other than dopamine

Question 5

what kind of study is Carlsson et al ?

Answer 5

review of research - not an investigative study

Question 6

Laruelle et al. 1996

Answer 6

found amphetamine use enhanced the release of dopamine significantly more in drug naive sz patients than age matched controls

this elevation correlates with the inducing of positive symptoms

Question 7

Lodge 1989

Answer 7

NMDA antagonists are psychostimulants in rodents and mimics the symptoms of psychosis in humans

glutamate activity at NMDA receptors produces psychotic reactions in rats and humans

Question 8

Miller and Abercrombie

Answer 8

tested on rodents
when given them an NMDA antagonist there is a slight increase in dopamine levels

release of dopamine is increased if glutamate activity is reduced

Question 9

Lindestrom 1997

Answer 9

PET scans found an abnormal turnover of dopamine in the brain of drug naive sz patients compared to the age matched controls

Question 10

Laurelle et al. 1999

Answer 10

patients with sz in remission had normal dopamine activity

Question 11

what is the role of glutamate

Answer 11

regulates dopamine levels
accelerator or a brake

Question 12

what symptoms is glutamate failure in the cerebral cortex suggested to lead to

Answer 12

negative symptoms

Question 13

what symptoms is glutamate failure in the basal ganglia suggested to lead to

Answer 13

positive symptoms

Question 14

what is the dopamine hypothesis

Answer 14

the theory that schizophrenia is caused by having too much dopamine in key areas of the brain

Question 15

what is the role of dopamine

Answer 15

to regulate mood and attention

Question 16

what is the role of glutamate

Answer 16

responsible for memory and learning

Question 17

results - dopamine hypothesis revisited

Answer 17

schizophrenic patients show more dopamine activity than a healthy control group

Laurelle et al. 1996 - amphetamine use enhances the release of dopamine more in drug naive sz patients then in age matched controls

Question 18

results - beyond dopamine, other NT’s

Answer 18

excess dopamine is likely to be too simplistic

PCP and ketamine produce psychotic symptoms - antagonists of NDMA receptors

Lodge et al. (1989) - different NMDA antagonists appear to induce psychotic symptoms in rodents and humans

Question 19

results - glutamatergic control of dopamine release

Answer 19

glutamate regulates dopamine activity

Miller and Abercrombie (1996) - release of dopamine is increased if glutamate activity is reduced (gave rodents an NMDA antagonist causing a slight increase in dopamine levels)

Question 19

results - glutamate dopamine interaction

Answer 19

????

Question 20

The Thalamic filter

Answer 20

the thalamus ‘filters off’ neurotransmitters coming out of the stratium

stops the cerebral cortex overloading

two pathways through the thalamus (direct and indirect)

Question 21

indirect pathway through the thalamus

Answer 21

hyperdopaminergia or hypoglutamatergia reduces the protective influence of the thalmus

links to positive symptoms

Question 22

direct pathway through the thalamus

Answer 22

abnormal glutamate and dopamine activity will excite the thalamus, starving the cerebral cortex of stimulation

links to negative symptoms

Question 23

results - comparing two sz models

Answer 23

research reviewed led to two different models for schizophrenia

hyperdopaminergic model - traditional view - increased dopamine leads to psychotic symptoms

hypoglutamatergic model - glutamate can produce an increase or decrease in dopamine activity

Question 24

results - is the therapeutic potential of dopaminergic agents exhausted - should glutamates be focused on instead?

Answer 24

Carlsson et al. are researching new drugs which regulate dopamine activity without producing harmful hypodopaminergia

• act at the pre synapse
• stop the brain producing too much dopamine
• in clinical trials

Question 25

conclusions

Answer 25

sz may have different types

could be caused by abnormal levels of different neurotransmitters (glutamate deficiency & elevated serotonin) and not just dopamine

excess dopamine is too simplistic of an explanation

further research is needed in developing drugs that avoid negative side effects, possibly by considering the role of other neurotransmitters

Question 26

what does drug naive mean

Answer 26

a patient who has not received treatment with that particular drug