Open AccessBrexpiprazole has a low risk of dopamine D 2 receptor sensitization and inhibits rebound phenomena related to D 2 and serotonin 5‐HT 2A receptors in rats
Author(s) -
Amada Naoki,
Akazawa Hitomi,
Ohgi Yuta,
Maeda Kenji,
Sugino Haruhiko,
Kurahashi Nobuyuki,
Kikuchi Tetsuro,
Futamura Takashi
Publication year - 2019
Publication title -
neuropsychopharmacology reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.661
H-Index - 13
ISSN - 2574-173X
DOI - 10.1002/npr2.12076
Subject(s) - apomorphine , stereotypy , pharmacology , agonist , chemistry , haloperidol , risperidone , partial agonist , dopamine receptor d2 , olanzapine , ritanserin , antipsychotic , 5 ht receptor , dopamine , endocrinology , psychology , medicine , receptor , serotonin , schizophrenia (object oriented programming) , psychiatry , amphetamine , biochemistry
Background Long‐term antipsychotic treatment in patients with schizophrenia can induce supersensitivity psychosis and tardive dyskinesia which is thought to be caused by dopamine D 2 receptor sensitization. We evaluated the effects of brexpiprazole on D 2 receptor sensitivity after subchronic treatment in rats. We also evaluated whether brexpiprazole could suppress enhanced response to D 2 receptors in rats subchronically dosed with another atypical antipsychotic. Methods The maximum D 2 receptor density ( B max ) and apomorphine (a D 2 receptor agonist)‐induced stereotypy were measured in rats orally dosed with vehicle, haloperidol (1 mg/kg), or brexpiprazole (4 or 30 mg/kg for B max , 6 or 30 mg/kg for stereotypy) for 21 days. Then, effects of oral administrations of brexpiprazole (3 mg/kg), aripiprazole (10 mg/kg), and olanzapine (3 mg/kg) against increases in apomorphine‐induced hyperlocomotion and (±)‐2,5‐dimethoxy‐4‐iodoamphetamine hydrochloride (DOI: a 5‐HT 2A receptor agonist)‐induced head twitches were evaluated in rats subcutaneously treated with risperidone (1.5 mg/kg/d) via minipumps for 21 days. Results Haloperidol and brexpiprazole (30 mg/kg: approximately tenfold ED 50 of anti‐apomorphine‐induced stereotypy) but not brexpiprazole (4 or 6 mg/kg) significantly increased the B max and apomorphine‐induced stereotypy. Brexpiprazole (3 mg/kg) and olanzapine (3 mg/kg) significantly suppressed both increases in apomorphine‐induced hyperlocomotion and also DOI‐induced head twitches in rats subchronically treated with risperidone, but aripiprazole (10 mg/kg) significantly suppressed only apomorphine‐induced hyperlocomotion. Conclusion Brexpiprazole has a low risk of D 2 receptor sensitization after a repeated administration and suppresses the rebound phenomena related to D 2 and 5‐HT 2A receptors after a repeated administration of risperidone.