title: Prevention of the phencyclidine-induced impairment in novel object recognition in female rats by co-administration of lurasidone or tandospirone, a 5-HT(1A) partial agonist.
abstract: Hypoglutamatergic function may contribute to cognitive impairment in schizophrenia (CIS). Subchronic treatment with the N-methyl-D-aspartate receptor antagonist, phencyclidine (PCP), induces enduring deficits in novel object recognition (NOR) in rodents. Acute treatment with atypical antipsychotic drugs (APDs), which are serotonin (5-HT)(2A)/dopamine D(2) antagonists, but not typical APDs, eg, haloperidol, reverses the PCP-induced NOR deficit in rats. We have tested the ability of lurasidone, an atypical APD with potent 5-HT(1A) partial agonist properties, tandospirone, a selective 5-HT(1A) partial agonist, haloperidol, a D(2) antagonist, and pimavanserin, a 5-HT(2A) inverse agonist, to prevent the development of the PCP-induced NOR deficit. Rats were administered lurasidone (0.1 or 1 mg/kg), tandospirone (5 mg/kg), pimavanserin (3 mg/kg), or haloperidol (1 mg/kg) b.i.d. 30 min before PCP (2 mg/kg, b.i.d.) for 7 days (day1-7), followed by a 7-day washout (day 8-14). Subchronic treatment with PCP induced an enduring NOR deficit. Lurasidone (1 mg/kg) but not 0.1 mg/kg, which is effective to acutely reverse the deficit due to subchronic PCP, or tandospirone, but not pimavanserin or haloperidol, significantly prevented the PCP-induced NOR deficit on day 15. The ability of lurasidone co-treatment to prevent the PCP-induced NOR deficit was enduring and still present at day 22. The preventive effect of lurasidone was blocked by WAY100635, a selective 5-HT(1A) antagonists, further evidence for the importance of 5-HT(1A) receptor stimulation in the NOR deficit produced by subchronic PCP. Further study is needed to determine whether these results concerning mechanism and dosage can be the basis for prevention of the development of CIS in at risk populations.
authors: Division of Psychopharmacology, Vanderbilt University Medical Center, Nashville, TN, USA.
authors: Masakuni
authors: M
authors: Horiguchi
authors: Kayleen E
authors: KE
authors: Hannaway
authors: Adesewa E
authors: AE
authors: Adelekun
authors: Karu
authors: K
authors: Jayathilake
authors: Herbert Y
authors: HY
authors: Meltzer
mesh_terms: D000818:Animals; D003072:Cognition Disorders / Q000139:chemically induced / Q000517:prevention & control*; D004195:Disease Models, Animal; D065127:Dopamine D2 Receptor Antagonists; D005260:Female; D006220:Haloperidol / Q000627:therapeutic use; D054833:Isoindoles / Q000627:therapeutic use*; D000069056:Lurasidone Hydrochloride; D010622:Phencyclidine; D010879:Piperazines / Q000627:therapeutic use*; D010880:Piperidines / Q000627:therapeutic use; D011725:Pyridines; D011743:Pyrimidines / Q000627:therapeutic use*; D051381:Rats; D020318:Rats, Long-Evans; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D012559:Schizophrenia / Q000188:drug therapy*; D058825:Serotonin 5-HT1 Receptor Agonists / Q000627:therapeutic use*; D058829:Serotonin 5-HT1 Receptor Antagonists; D058826:Serotonin 5-HT2 Receptor Agonists / Q000627:therapeutic use; D013844:Thiazoles / Q000627:therapeutic use*; D014508:Urea / Q000031:analogs & derivatives / Q000627:therapeutic use
chemical_list: D065127:Dopamine D2 Receptor Antagonists; D054833:Isoindoles; D010879:Piperazines; D010880:Piperidines; D011725:Pyridines; D011743:Pyrimidines; D016194:Receptors, N-Methyl-D-Aspartate; D058825:Serotonin 5-HT1 Receptor Agonists; D058829:Serotonin 5-HT1 Receptor Antagonists; D058826:Serotonin 5-HT2 Receptor Agonists; D013844:Thiazoles; C055267:tandospirone; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; D014508:Urea; D010622:Phencyclidine; D006220:Haloperidol; C510793:pimavanserin; D000069056:Lurasidone Hydrochloride