Combined serotonin (5-HT)1A agonism, 5-HT2A and dopamine D2 receptor antagonism reproduces atypical antipsychotic drug effects on phencyclidine-impaired novel object recognition in rats

2015 ◽  
Vol 285 ◽  
pp. 165-175 ◽  
Author(s):  
Yoshihiro Oyamada ◽  
Masakuni Horiguchi ◽  
Lakshmi Rajagopal ◽  
Masanori Miyauchi ◽  
Herbert Y. Meltzer
2017 ◽  
Vol 31 (4) ◽  
pp. 442-452 ◽  
Author(s):  
Masanori Miyauchi ◽  
Nichole M Neugebauer ◽  
Herbert Y Meltzer

Several atypical antipsychotic drugs (APDs) have high affinity for the dopamine (DA) D4 receptor, but the relevance to the efficacy for the treatment of cognitive impairment associated with schizophrenia (CIAS) is poorly understood. The aim of this study was to investigate the effects of D4 receptor stimulation or blockade on novel object recognition (NOR) in normal rats and on the sub-chronic phencyclidine (PCP)-induced novel object recognition deficit. The effect of the D4 agonist, PD168077, and the D4 antagonist, L-745,870, were studied alone, and in combination with clozapine and lurasidone. In normal rats, L-745,870 impaired novel object recognition, whereas PD168077 had no effect. PD168077 acutely reversed the sub-chronic phencyclidine-induced novel object recognition deficit. Co-administration of a sub-effective dose (SED) of PD168077 with a sub-effective dose of lurasidone also reversed this deficit, but a sub-effective dose of PD168077 with a sub-effective dose of clozapine, a more potent D4 antagonist than lurasidone, did not reverse the sub-chronic phencyclidine-induced novel object recognition deficit. At a dose that did not induce a novel object recognition deficit, L-745,870 blocked the ability of clozapine, but not lurasidone, to reverse the novel object recognition deficit. D4 receptor agonism has a beneficial effect on novel object recognition in sub-chronic PCP-treated rats and augments the cognitive enhancing efficacy of an atypical antipsychotic drug that lacks affinity for the D4 receptor, lurasidone.


2018 ◽  
Vol 155 ◽  
pp. 249-260 ◽  
Author(s):  
Karina Vidarte Gaspary ◽  
Gustavo Kellermann Reolon ◽  
Darlan Gusso ◽  
Carla Denise Bonan

Sign in / Sign up

Export Citation Format

Share Document