Effect of amphetamine, α-methyl-p-tyrosine (α-MPT) and antipsychotic agents on dopamine D₂-type receptor occupancy in rats

1. EEDQ inactivates unoccupied receptors in vivo in brain tissue and is useful in determining which receptors are occupied by a drug treatment. 2. α-MPT, inhibits the synthesis of dopamine, reducing D₂-type receptor occupancy by dopamine and enhances the amount of receptor inactivation by EEDQ. 3. Amphetamine releases dopamine resulting in increased occupancy of dopamine D₂-type receptors and we have shown that it protects those receptors from EEDQ. 4. Clozapine and remoxipride, two antipsychotic agents, occupied the dopamine receptors in both the caudate and cortex. 5. These findings are important because they substantiate other results obtained with amphetamine and SPECT, which demonstrated an exaggerated dopamine neurotransmission in schizophrenic patients versus normal controls.