Dopamine and positive symptoms

Question 1

Pharmacological evidence indicates over activation of

Answer 1

DA in mesolimbic pathway is responsible of positive sxs of schizo

Question 2

Chlorpromazine (thorazine) was the first…others eliminated or reduced positive symtoms of schiz, impacting…

Answer 2

All these drugs blocked D2 and D3 dopamine receptors

Question 3

Substances that act as dopamine agonists produce

Answer 3

hallucinations and delusions: 1. amphetamine, cocaine produce psychotic sxs. at high enough levels
2. L-dopa given for Parkinson’s and other dopamine agonists produce psychotic sxs. at high enough levels

Question 4

Mesolimbic projects from….to….and…

Answer 4

Mesolimbic projects from ventral tegmental area to nucleus accumbens and amygdala

Question 5

Mesolimbic projects from ventral tegmental area to nucleus accumbens and amygdala

Answer 5

1. most experts believe mesolimbic is the dopamine system involved in sch.
2. n.a. very important in reinforcement (self-stimulation in rats)
3. possibly overactivity of dopamine in this area results in “reinforcing” neural activity occurring simultaneously with irrational thoughts, and through this reinforcement irrational thoughts develop into delusions
4. remember, any brain activity that occurs when dopamine is released increases in frequency
5. it is thought paranoid delusions may arise from overactivation of the amygdala in much the same way

Question 6

DA abnormality in schizo brains…

Answer 6

1. Increased release of DA
2. PET shows amphetamine causes release of more dopamine in striatum sch. s’s than controls
3. even though the mesolimbic system is thought to be involved, the thinking apparently is that if the DA neurons in the striatum are hyper, the DA neurons in the mesolimbic system likely are also
4. the greater the amount of DA release the greater the extent of positive sxs.

Question 7

Long-term drug use

Answer 7

1. Side effects of “classic” (old) antipsychotic meds
2. Parkinson’s sxs. – slowness of movement, lack of facial expression – usually temporary
3. Breast development due to increased prolactin activity
4. ANS sxs. i.e. dry mouth
5. tardive dyskinesia
   - occurs in ~ 1/3 of patients
   - usually occurs after prolonged use of anti-psychotics
   - facial tics, tongue protrusions, check puffing, lip pursing
   - caused by over-activity of dopamine synapses in striatum due to supersensitivity – increased sensitivity to dopamine that occurs as an apparent compensation when antagonist drug is administered

Question 8

“Atypical antipsychotic” drugs are more specific in the DA receptors they affect

Answer 8

1. have less problems with t.d.

2. reduce positive and negative sxs