Diminished catalepsy and dopamine metabolism distinguish aripiprazole from haloperidol or risperidone.
Catalepsy and changes in striatal and limbic dopamine metabolism were investigated in mice after oral administration of aripiprazole, haloperidol, and risperidone. Catalepsy duration decreased with chronic (21 day) aripiprazole compared with acute (single dose) treatment across a wide dose range, whereas catalepsy duration persisted with chronic haloperidol treatment. At the time of maximal catalepsy, acute aripiprazole did not alter neostriatal dopamine metabolite/dopamine ratios or homovanillic acid (HVA) levels, and produced small increases in dihydroxyphenylacetic acid (DOPAC). Effects were similar in the olfactory tubercle. Dopamine metabolism was essentially unchanged in both regions after chronic aripiprazole. Acute treatments with haloperidol or risperidone elevated DOPAC, HVA, and metabolite/dopamine ratios in both brain areas and these remained elevated with chronic treatment. The subtle effects of aripiprazole on striatal and limbic dopamine metabolism, and the decrease in catalepsy with chronic administration, illustrate fundamental differences in dopamine neurochemical actions and behavioral sequelae of aripiprazole compared to haloperidol or risperidone.
Nakai
Satoru
S
Second Institute of New Drug Research, Otsuka Pharmaceutical Co. Ltd., 463-10 Kagasuno, Kawauchi, Tokushima 771-0192, Japan. s_nakai@research.otsuka.co.jp
Hirose
Tsuyoshi
T
Uwahodo
Yasufumi
Y
Imaoka
Takeshi
T
Okazaki
Hiroshi
H
Miwa
Takashi
T
Nakai
Masami
M
Yamada
Sakiko
S
Dunn
Bob
B
Burris
Kevin D
KD
Molinoff
Perry B
PB
Tottori
Katsura
K
Altar
C Anthony
CA
Kikuchi
Tetsuro
T
D000284:Administration, Oral; D000818:Animals; D014150:Antipsychotic Agents / Q000633:toxicity*; D000068180:Aripiprazole; D002375:Catalepsy / Q000139:chemically induced / Q000378:metabolism*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D006220:Haloperidol / Q000633:toxicity; D008032:Limbic System / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010879:Piperazines / Q000633:toxicity; D015363:Quinolones / Q000633:toxicity; D018967:Risperidone / Q000633:toxicity; D013997:Time Factors
D014150:Antipsychotic Agents; D010879:Piperazines; D015363:Quinolones; D000068180:Aripiprazole; D006220:Haloperidol; D018967:Risperidone; D004298:Dopamine