Dopamine receptor sensitivity

In the experimental model test animals are given neuroleptics for a period of several weeks. If the drug is withdrawn a dopamine receptor supersensitivity sets in.

If in such a situation a dopamine antagonist is introduced, stereotypical behavior appears. This condition is called behavioral sensitivity.

The reason for the sensitivity is receptor proliferation (increased production) due to chronic receptor blockage.

The following instruments are used in the research:

– SCH23390 (Selective D1 receptor antagonist)
– SKF38393 (Selective D1 receptor agonist)
– Raclopride (Selective D2 receptor antagonist)
– LY171555 (Selective D2 receptor agonist)

Catalepsy

Immobility associated with antidopaminergic/antipsychotic drugs.
Both D1 and D2 antagonists can cause this. Using them together creates a synergic effect.

Measuring Catalepsy

The measuring is undertaken on the 1st and 21st day of drug use. It is assessed how many minutes the animal whose front legs are placed on a vertical bar, can hold this position.

Measuring Stereotype

– Animals that have continuously been given neuroleptics are injected with apomorphine (a dopamine agonist).
– 0=normal behavior
– 1=constant loco-motor movement; rearing (movement towards the tail), sniffing, licking absent.
– 2=medium loco-motor movement. Continuous sniffing.
– 3=intermittent loco-motor activity
– 4=constant licking, gnawing biting, infrequent loco-motor activity.

Autoradiography

– Receptor ligands bound with Iodine 125 are used (SCH 23982 for D1, Sulpiride for D2).
– Applied to 20 micrometer brain sections.
– After a certain period of incubation it is brought into contact with the film.
– Finally the striatal area on the film is measured with an optic dansitometer.

Rotational Movement

– Created by the effect of antagonist D1 and D2.

Questions on the Receptor Theory

– Negative PET findings
– Why relapse?
– Why resistance to treatment?

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