Effect of amphetamine, alpha-methyl-p-tyrosine (alpha-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. alpha-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.
Lahti
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RA
Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, USA. rlahti@umaryland.edu
Tamminga
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CA
D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001667:Binding, Competitive; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000502:physiology*; D015899:Tomography, Emission-Computed, Single-Photon; D019805:alpha-Methyltyrosine / Q000494:pharmacology*
D014150:Antipsychotic Agents; D000697:Central Nervous System Stimulants; D004791:Enzyme Inhibitors; D017448:Receptors, Dopamine D2; D019805:alpha-Methyltyrosine; D000661:Amphetamine