TY - JOUR
T1 - Atypical antipsychotic drugs, quetiapine, iloperidone, and melperone, preferentially increase dopamine and acetylcholine release in rat medial prefrontal cortex
T2 - Role of 5-HT1A receptor agonism
AU - Ichikawa, Junji
AU - Li, Zhu
AU - Dai, Jin
AU - Meltzer, Herbert Y.
N1 - Funding Information:
This study was supported, in part, by grants from the Ritter Foundation, the Warren Foundation, Mr Donald Test, AstraZeneca and Novartis. We are grateful to Ms Anna R. Alboszta for an excellent technical assistance.
PY - 2002/11/29
Y1 - 2002/11/29
N2 - Preferential increases in both cortical dopamine (DA) and acetylcholine (ACh) release have been proposed to distinguish the atypical antipsychotic drugs (APDs) clozapine, olanzapine, risperidone and ziprasidone from typical APDs such as haloperidol. Although only clozapine and ziprasidone are directly acting 5-HT1A agonists, WAY100635, a selective 5-HT1A antagonist, partially attenuates these atypical APD-induced increases in cortical DA release that may be due to combined 5-HT2A and D2 blockade. However, WAY100635 does not attenuate clozapine-induced cortical ACh release. The present study determined whether quetiapine, iloperidone and melperone, 5-HT2A/D2 antagonist atypical APDs, also increase cortical DA and ACh release, and whether these effects are related to 5-HT1A agonism. Quetiapine (30 mg/kg), iloperidone (1-10 mg/kg), and melperone (3-10 mg/kg) increased DA and ACh release in the medial prefrontal cortex (mPFC). Iloperidone (10 mg/kg) and melperone (10 mg/kg), but not quetiapine (30 mg/kg), produced an equivalent or a smaller increase in DA release in the nucleus accumbens (NAC), respectively, compared to the mPFC, whereas none of them increased ACh release in the NAC. WAY100635 (0.2 mg/kg), which alone did not affect DA or ACh release, partially attenuated quetiapine (30 mg/kg)-, iloperidone (10 mg/kg)- and melperone (10 mg/kg)-induced DA release in the mPFC. WAY100635 also partially attenuated quetiapine (30 mg/kg)-induced ACh release in the mPFC, but not that induced by iloperidone (10 mg/kg) or melperone (10 mg/kg). These results indicate that quetiapine, iloperidone and melperone preferentially increase DA release in the mPFC, compared to the NAC via a 5-HT1A-related mechanism. However, 5-HT1A agonism may be important only for quetiapine-induced ACh release.
AB - Preferential increases in both cortical dopamine (DA) and acetylcholine (ACh) release have been proposed to distinguish the atypical antipsychotic drugs (APDs) clozapine, olanzapine, risperidone and ziprasidone from typical APDs such as haloperidol. Although only clozapine and ziprasidone are directly acting 5-HT1A agonists, WAY100635, a selective 5-HT1A antagonist, partially attenuates these atypical APD-induced increases in cortical DA release that may be due to combined 5-HT2A and D2 blockade. However, WAY100635 does not attenuate clozapine-induced cortical ACh release. The present study determined whether quetiapine, iloperidone and melperone, 5-HT2A/D2 antagonist atypical APDs, also increase cortical DA and ACh release, and whether these effects are related to 5-HT1A agonism. Quetiapine (30 mg/kg), iloperidone (1-10 mg/kg), and melperone (3-10 mg/kg) increased DA and ACh release in the medial prefrontal cortex (mPFC). Iloperidone (10 mg/kg) and melperone (10 mg/kg), but not quetiapine (30 mg/kg), produced an equivalent or a smaller increase in DA release in the nucleus accumbens (NAC), respectively, compared to the mPFC, whereas none of them increased ACh release in the NAC. WAY100635 (0.2 mg/kg), which alone did not affect DA or ACh release, partially attenuated quetiapine (30 mg/kg)-, iloperidone (10 mg/kg)- and melperone (10 mg/kg)-induced DA release in the mPFC. WAY100635 also partially attenuated quetiapine (30 mg/kg)-induced ACh release in the mPFC, but not that induced by iloperidone (10 mg/kg) or melperone (10 mg/kg). These results indicate that quetiapine, iloperidone and melperone preferentially increase DA release in the mPFC, compared to the NAC via a 5-HT1A-related mechanism. However, 5-HT1A agonism may be important only for quetiapine-induced ACh release.
KW - 5-HT receptor
KW - Dopamine and acetylcholine release
KW - Iloperidone
KW - Medial prefrontal cortex and nucleus accumbens
KW - Melperone
KW - Quetiapine
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UR - http://www.scopus.com/inward/citedby.url?scp=0037195552&partnerID=8YFLogxK
U2 - 10.1016/S0006-8993(02)03570-9
DO - 10.1016/S0006-8993(02)03570-9
M3 - Article
C2 - 12445705
AN - SCOPUS:0037195552
VL - 956
SP - 349
EP - 357
JO - Brain Research
JF - Brain Research
SN - 0006-8993
IS - 2
ER -