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Positive modulation of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors reverses sub-chronic PCP-induced deficits in the novel object recognition task in rats.
Behav Brain Res. 2010 Feb 11; 207(1):144-50.BB

Abstract

Cognitive deficits are a major clinical unmet need in schizophrenia. The psychotomimetic drug phencyclidine (PCP) is widely applied in rodents to mimic symptoms of schizophrenia, including cognitive deficits. Previous studies have shown that sub-chronic PCP induces an enduring episodic memory deficit in female Lister Hooded rats in the novel object recognition (NOR) task. Here we show that positive modulation of AMPA receptor (AMPAR) mediated glutamate transmission alleviates cognitive deficits induced by sub-chronic PCP treatment. Female Lister hooded rats were treated sub-chronically with either vehicle (0.9% saline) or PCP (2mg/kg two doses per day for 7 days), followed by a 7 days washout period. 30 min prior to the acquisition trial of the NOR task animals were dosed with either vehicle, CX546 (10, 40 or 80 mg/kg) or CX516 (0.5, 2.5, 10, 40 or 80 mg/kg). Our results show that sub-chronic PCP treatment induced a significant decrease in the discrimination index (DI) and both ampakines CX546 and CX516 were able to reverse this disruption of object memory in rats in the novel object recognition task. These data suggest that positive AMPAR modulation may represent a mechanism for treatment of cognitive deficits in schizophrenia.

Authors+Show Affiliations

H. Lundbeck A/S, Discovery Pharmacology Research-Cognition, Ottiliavej 9, Valby, Denmark. tdn@lundbeck.comNo 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

19822174

Citation

Damgaard, Trine, et al. "Positive Modulation of Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid (AMPA) Receptors Reverses Sub-chronic PCP-induced Deficits in the Novel Object Recognition Task in Rats." Behavioural Brain Research, vol. 207, no. 1, 2010, pp. 144-50.
Damgaard T, Larsen DB, Hansen SL, et al. Positive modulation of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors reverses sub-chronic PCP-induced deficits in the novel object recognition task in rats. Behav Brain Res. 2010;207(1):144-50.
Damgaard, T., Larsen, D. B., Hansen, S. L., Grayson, B., Neill, J. C., & Plath, N. (2010). Positive modulation of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors reverses sub-chronic PCP-induced deficits in the novel object recognition task in rats. Behavioural Brain Research, 207(1), 144-50. https://doi.org/10.1016/j.bbr.2009.09.048
Damgaard T, et al. Positive Modulation of Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid (AMPA) Receptors Reverses Sub-chronic PCP-induced Deficits in the Novel Object Recognition Task in Rats. Behav Brain Res. 2010 Feb 11;207(1):144-50. PubMed PMID: 19822174.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Positive modulation of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors reverses sub-chronic PCP-induced deficits in the novel object recognition task in rats. AU - Damgaard,Trine, AU - Larsen,Dorrit Bjerg, AU - Hansen,Suzanne L, AU - Grayson,Ben, AU - Neill,Jo C, AU - Plath,Niels, Y1 - 2009/10/12/ PY - 2009/03/10/received PY - 2009/09/28/revised PY - 2009/09/30/accepted PY - 2009/10/14/entrez PY - 2009/10/14/pubmed PY - 2010/1/15/medline SP - 144 EP - 50 JF - Behavioural brain research JO - Behav Brain Res VL - 207 IS - 1 N2 - Cognitive deficits are a major clinical unmet need in schizophrenia. The psychotomimetic drug phencyclidine (PCP) is widely applied in rodents to mimic symptoms of schizophrenia, including cognitive deficits. Previous studies have shown that sub-chronic PCP induces an enduring episodic memory deficit in female Lister Hooded rats in the novel object recognition (NOR) task. Here we show that positive modulation of AMPA receptor (AMPAR) mediated glutamate transmission alleviates cognitive deficits induced by sub-chronic PCP treatment. Female Lister hooded rats were treated sub-chronically with either vehicle (0.9% saline) or PCP (2mg/kg two doses per day for 7 days), followed by a 7 days washout period. 30 min prior to the acquisition trial of the NOR task animals were dosed with either vehicle, CX546 (10, 40 or 80 mg/kg) or CX516 (0.5, 2.5, 10, 40 or 80 mg/kg). Our results show that sub-chronic PCP treatment induced a significant decrease in the discrimination index (DI) and both ampakines CX546 and CX516 were able to reverse this disruption of object memory in rats in the novel object recognition task. These data suggest that positive AMPAR modulation may represent a mechanism for treatment of cognitive deficits in schizophrenia. SN - 1872-7549 UR - https://www.unboundmedicine.com/medline/citation/19822174/Positive_modulation_of_alpha_amino_3_hydroxy_5_methyl_4_isoxazolepropionic_acid__AMPA__receptors_reverses_sub_chronic_PCP_induced_deficits_in_the_novel_object_recognition_task_in_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0166-4328(09)00594-4 DB - PRIME DP - Unbound Medicine ER -