Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
-
Neuropsychopharmacology · Oct 2001
Comparative StudyCortical responsiveness during talking and listening in schizophrenia: an event-related brain potential study.
Failures to recognize inner speech as self-generated may underlie positive symptoms of schizophrenia-like auditory hallucinations. This could result from a faulty comparison in auditory cortex between speech-related corollary discharge and reafferent discharges from thinking or speaking, with misattribution of internal thoughts to external sources. Although compelling, failures to monitor covert speech (thoughts) are not as amenable to investigation as failures to monitor overt speech (talking). ⋯ Although the failure of N1 to be reduced during talking was not related to current hallucinations in patients, it may be related to the potential to hallucinate.
-
Neuropsychopharmacology · Oct 2001
Evaluation of dopamine D-2 receptor occupancy by clozapine, risperidone, and haloperidol in vivo in the rodent and nonhuman primate brain using 18F-fallypride.
We have used the high-affinity dopamine D-2 receptor radioligand, 18F-fallypride for evaluating receptor occupancy by the antipsychotic drugs, clozapine, risperidone, and haloperidol in rodents and nonhuman primates. In rodents, clozapine (0.1 mg/kg to 100 mg/kg) competed with 18F-fallypride at all the doses administered. At doses over 40 mg/kg, clozapine was able to displace all the administered 18F-fallypride. ⋯ Dopamine D-2 receptor occupancy in the monkeys was studied using positron emission tomography (PET) after acute subcutaneous doses of the various drugs. At therapeutically relevant doses, clozapine, risperidone, and haloperidol were able to compete significantly with the binding of 18F-fallypride in all brain regions in rhesus monkeys, and our analyses indicate that these drugs (clozapine, risperidone, and haloperidol) do not discriminate between the striatal (caudate and putamen) and the extrastriatal (thalamus and cortical regions) dopamine receptors. The following extent of D-2 receptor occupancies were measured in the monkey brain using PET: clozapine approximately 70% (dose of 9.7 mg/kg), risperidone approximately 75% (0.05 mg/kg), and haloperidol approximately 90% (0.05 mg/kg).