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D(1) receptor agonists reverse the subchronic phencyclidine (PCP)-induced novel object recognition (NOR) deficit in female rats.
Behav Brain Res. 2013 Feb 01; 238:36-43.BB

Abstract

Development of dopamine (DA) D(1) receptor agonists is a priority to improve cognitive impairment in schizophrenia (CIS). This study examined the dose-response relationship of the selective D(1) agonist, SKF38393 (0.5-40 mg/kg), to reverse the deficit in novel object recognition (NOR), an analog of declarative memory in man, produced by subchronic phencyclidine (PCP), an N-methyl-D-aspartate (NMDA) receptor non-competitive antagonist, and the ability of the D(1) antagonists, SCH23390 (0.05 mg/kg) and SKF83566 (0.15 mg/kg), to impair NOR in normal Long-Evans female rats. We also examined the ability of tandospirone, a serotonin (5-HT)(1A) receptor partial agonist, and LY341495, a mGluR2/3 receptor antagonist, to potentiate or block the effects of SKF38393 on NOR, respectively. SKF38393 reversed the persistent NOR deficit produced by subchronic PCP; the dose-response curve for SKF38393 was an inverted U-shape, with the peak effect at 6 mg/kg. SKF83566 and SCH23390 impaired NOR in normal rats. Co-administration of sub-effective doses of SKF38393 (0.25 mg/kg) and tandospirone (0.2 mg/kg) improved the PCP-induced NOR deficit, while LY341495 (1 mg/kg) blocked the ameliorating effect of SKF38393 (6 mg/kg), respectively. These data provide the first evidence that the reversal of the PCP-induced NOR deficit by D(1) agonism has an inverted U-shaped dose-response curve and that 5-HT(1A) and mGluR2/3 receptor signalling facilitates the efficacy of D(1) agonism to improve these deficits. These data suggest that although D(1) agonists may be useful to improve CIS, these agents, particularly higher doses, may also worsen cognitive function in some patients, because of an inverted U-shaped dose response curve.

Authors+Show Affiliations

Division of Psychopharmacology, Vanderbilt University Medical Center, Nashville, TN 37212, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23018127

Citation

Horiguchi, Masakuni, et al. "D(1) Receptor Agonists Reverse the Subchronic Phencyclidine (PCP)-induced Novel Object Recognition (NOR) Deficit in Female Rats." Behavioural Brain Research, vol. 238, 2013, pp. 36-43.
Horiguchi M, Hannaway KE, Adelekun AE, et al. D(1) receptor agonists reverse the subchronic phencyclidine (PCP)-induced novel object recognition (NOR) deficit in female rats. Behav Brain Res. 2013;238:36-43.
Horiguchi, M., Hannaway, K. E., Adelekun, A. E., Huang, M., Jayathilake, K., & Meltzer, H. Y. (2013). D(1) receptor agonists reverse the subchronic phencyclidine (PCP)-induced novel object recognition (NOR) deficit in female rats. Behavioural Brain Research, 238, 36-43. https://doi.org/10.1016/j.bbr.2012.09.030
Horiguchi M, et al. D(1) Receptor Agonists Reverse the Subchronic Phencyclidine (PCP)-induced Novel Object Recognition (NOR) Deficit in Female Rats. Behav Brain Res. 2013 Feb 1;238:36-43. PubMed PMID: 23018127.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - D(1) receptor agonists reverse the subchronic phencyclidine (PCP)-induced novel object recognition (NOR) deficit in female rats. AU - Horiguchi,Masakuni, AU - Hannaway,Kayleen E, AU - Adelekun,Adesewa E, AU - Huang,Mei, AU - Jayathilake,Karu, AU - Meltzer,Herbert Y, Y1 - 2012/09/24/ PY - 2012/02/21/received PY - 2012/09/14/revised PY - 2012/09/18/accepted PY - 2012/9/29/entrez PY - 2012/9/29/pubmed PY - 2013/5/18/medline SP - 36 EP - 43 JF - Behavioural brain research JO - Behav Brain Res VL - 238 N2 - Development of dopamine (DA) D(1) receptor agonists is a priority to improve cognitive impairment in schizophrenia (CIS). This study examined the dose-response relationship of the selective D(1) agonist, SKF38393 (0.5-40 mg/kg), to reverse the deficit in novel object recognition (NOR), an analog of declarative memory in man, produced by subchronic phencyclidine (PCP), an N-methyl-D-aspartate (NMDA) receptor non-competitive antagonist, and the ability of the D(1) antagonists, SCH23390 (0.05 mg/kg) and SKF83566 (0.15 mg/kg), to impair NOR in normal Long-Evans female rats. We also examined the ability of tandospirone, a serotonin (5-HT)(1A) receptor partial agonist, and LY341495, a mGluR2/3 receptor antagonist, to potentiate or block the effects of SKF38393 on NOR, respectively. SKF38393 reversed the persistent NOR deficit produced by subchronic PCP; the dose-response curve for SKF38393 was an inverted U-shape, with the peak effect at 6 mg/kg. SKF83566 and SCH23390 impaired NOR in normal rats. Co-administration of sub-effective doses of SKF38393 (0.25 mg/kg) and tandospirone (0.2 mg/kg) improved the PCP-induced NOR deficit, while LY341495 (1 mg/kg) blocked the ameliorating effect of SKF38393 (6 mg/kg), respectively. These data provide the first evidence that the reversal of the PCP-induced NOR deficit by D(1) agonism has an inverted U-shaped dose-response curve and that 5-HT(1A) and mGluR2/3 receptor signalling facilitates the efficacy of D(1) agonism to improve these deficits. These data suggest that although D(1) agonists may be useful to improve CIS, these agents, particularly higher doses, may also worsen cognitive function in some patients, because of an inverted U-shaped dose response curve. SN - 1872-7549 UR - https://www.unboundmedicine.com/medline/citation/23018127/D_1__receptor_agonists_reverse_the_subchronic_phencyclidine__PCP__induced_novel_object_recognition__NOR__deficit_in_female_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0166-4328(12)00616-X DB - PRIME DP - Unbound Medicine ER -