Long-term effects of cariprazine exposure on dopamine receptor subtypes.
BACKGROUND
All clinically effective antipsychotics are known to act on the dopaminergic system, and previous studies have demonstrated that repeated treatment with antipsychotics produced region-specific changes in dopamine receptor levels. Cariprazine is a dopamine D₃ and D₂ receptor partial agonist with preferential binding to D₃ receptors. We examined the effects of chronic cariprazine administration on dopamine receptor levels.


METHODS
Rats were administered either vehicle or cariprazine (0.06, 0.2, or 0.6 mg/kg) for 28 days. Dopamine receptor levels were quantitated using autoradiographic assays on brain tissue sections from the medial prefrontal cortex (mPFC), nucleus accumbens (NAc), caudate putamen (CPu), hippocampus (HIPP), olfactory tubercle (OT), and islands of Calleja (ICj).


RESULTS
Chronic treatment with cariprazine did not alter D₁ receptor levels in any brain region tested. Cariprazine increased D₂ receptor levels in mPFC (27%-43%), NAc (40%-45%), medial (41%-53%) and lateral (52%-63%) CPu, and HIPP (38%). Cariprazine dose-dependently upregulated D₃ receptor levels in ICj (32%-57%), OT (27%-67%), and NAc shell (31%-48%). Repeated cariprazine treatment increased D₄ receptor in NAc (53%-82%), medial (54%-98%) and lateral (58%-74%) CPu, and HIPP (38%-98%).


CONCLUSIONS
Similar to other antipsychotics, cariprazine upregulated D₂ and D₄ receptor levels in various brain regions. Cariprazine was unique among antipsychotics in increasing D₃ receptor levels, which may support its unique psychopharmacologic properties.
1Department of Psychiatry & Neuroscience,Harvard Medical School and McLean Hospital,Belmont,Massachusetts,USA.
Yong Kee
YK
Choi
2Department of Pharmacology,Forest Research Institute,Jersey City,New Jersey,USA.
Nika
N
Adham
3Department of Pharmacological and Safety Research,Gedeon Richter Plc,Budapest,Hungary.
Béla
B
Kiss
4Department of Behavioral Pharmacology,Division of Pharmacology and Drug Safety Research,Gedeon Richter Plc,Budapest,Hungary.
István
I
Gyertyán
1Department of Psychiatry & Neuroscience,Harvard Medical School and McLean Hospital,Belmont,Massachusetts,USA.
Frank I
FI
Tarazi
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001552:Benzazepines / Q000493:pharmacokinetics; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects*; D018491:Dopamine Agonists / Q000493:pharmacokinetics; D018492:Dopamine Antagonists / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D008297:Male; D010879:Piperazines / Q000494:pharmacology*; D011485:Protein Binding / Q000187:drug effects; D011877:Radionuclide Imaging; D051381:Rats; D017207:Rats, Sprague-Dawley; D011954:Receptors, Dopamine / Q000378:metabolism*; D013764:Tetrahydronaphthalenes / Q000493:pharmacokinetics; D014316:Tritium / Q000493:pharmacokinetics
D014150:Antipsychotic Agents; D001552:Benzazepines; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D010879:Piperazines; D011954:Receptors, Dopamine; C534628:SCH 23390; D013764:Tetrahydronaphthalenes; D014316:Tritium; C533287:cariprazine; C031349:7-hydroxy-2-N,N-dipropylaminotetralin