DOI, a 5-HT2A/2C receptor agonist, attenuates clozapine-induced cortical dopamine release.
(+/-)-1-(2,5-Dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI, 1.25, 2.5 and 5 mg/kg), a serotonin (5-HT)2A/2C agonist, produced an inverted U-shaped increase in DA release in rat medial prefrontal cortex (mPFC) with a significant effect only at 2.5 mg/kg. This effect was completely abolished by M100907 (0.1 mg/kg), a 5-HT2A antagonist, and WAY100635 (0.2 mg/kg), a 5-HT1A antagonist, neither of which when given alone affected dopamine release. DOI (2.5 mg/kg), but not the 5-HT2C agonist Ro 60-0175 (3 mg/kg), attenuated clozapine (20 mg/kg)-induced mPFC dopamine release. These results suggest that 5-HT2A receptor stimulation increases basal cortical dopamine release via 5-HT1A receptor stimulation, and inhibits clozapine-induced cortical dopamine release by diminishing 5-HT2A receptor blockade.
Ichikawa
J
J
Division of Psychopharmacology, Departments of Psychiatry and Pharmacology, Vanderbilt University School of Medicine, Nashville, TN, USA. ichikaj@ctrvax.vanderbilt.edu
Dai
J
J
Meltzer
H Y
HY
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D003024:Clozapine / Q000037:antagonists & inhibitors*; D003864:Depression, Chemical; D004298:Dopamine / Q000378:metabolism*; D005464:Fluorobenzenes / Q000494:pharmacology; D007215:Indophenol / Q000031:analogs & derivatives / Q000494:pharmacology; D017551:Microdialysis; D010879:Piperazines / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D017397:Prefrontal Cortex / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044402:Receptor, Serotonin, 5-HT2A; D044405:Receptor, Serotonin, 5-HT2C; D011985:Receptors, Serotonin / Q000187:drug effects*; D044263:Receptors, Serotonin, 5-HT1; D012636:Secretory Rate / Q000187:drug effects; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*
D014150:Antipsychotic Agents; D005464:Fluorobenzenes; D010879:Piperazines; D010880:Piperidines; D011725:Pyridines; D044402:Receptor, Serotonin, 5-HT2A; D044405:Receptor, Serotonin, 5-HT2C; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; C113896:dimethoxy-4-indophenyl-2-aminopropane; D007215:Indophenol; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; C079049:volinanserin; D003024:Clozapine; D004298:Dopamine