Reversal of cognitive deficits by an ampakine (CX516) and sertindole in two animal models of schizophrenia--sub-chronic and early postnatal PCP treatment in attentional set-shifting

Brian Villumsen Broberg; Birte Yding Glenthøj; Rebecca Dias; Dorrit Bjerg Larsen; Christina Kurre Olsen; Brian Villumsen Broberg; Birte Yding Glenthøj; Rebecca Dias; Dorrit Bjerg Larsen; Christina Kurre Olsen

doi:10.1007/s00213-009-1540-5

Reversal of cognitive deficits by an ampakine (CX516) and sertindole in two animal models of schizophrenia--sub-chronic and early postnatal PCP treatment in attentional set-shifting

Brian Villumsen Broberg, Birte Yding Glenthøj, Rebecca Dias, Dorrit Bjerg Larsen, Christina Kurre Olsen, Brian Villumsen Broberg, Birte Yding Glenthøj, Rebecca Dias, Dorrit Bjerg Larsen, Christina Kurre Olsen

49 Citations (Scopus)

Abstract

RATIONALE: Therapies treating cognitive impairments in schizophrenia especially deficits in executive functioning are not available at present. OBJECTIVE: The current study evaluated the effect of ampakine CX516 in reversing deficits in executive functioning as represented in two animal models of schizophrenia and assessed by a rodent analog of the intradimensional-extradimensional (ID-ED) attentional set-shifting task. The second generation antipsychotic, sertindole, provided further validation of the schizophrenia-like disease models. METHODS: Animals were subjected to (a) sub-chronic or (b) early postnatal phencyclidine (PCP) treatment regimes: (a) Administration of either saline or PCP (5 mg/kg, intraperitonally b.i.d. for 7 days) followed by a 7-day washout period and testing on day 8. (b) On postnatal days (PNDs) 7, 9, and 11, rats were subjected to administration of either saline or PCP (20 mg/kg, subcutaneously (s.c.)) and tested on PNDs 56-95, after reaching adulthood. The single test session required rats to dig for food rewards in a series of discriminations following acute administration of either vehicle, or CX516 (5-40 mg/kg, s.c.), or sertindole (1.25 mg/kg, perorally). RESULTS: The specific extradimensional deficits produced by sub-chronic or early postnatal PCP treatment were significantly attenuated by sertindole and dose-dependently by CX516. CONCLUSION: Findings here further establish PCP treatment as model of executive functioning deficits related to schizophrenia and provide evidence that direct glutamatergic interventions could improve these, when assessed in the ID-ED attentional set-shifting task.

Original language	English
Journal	Psychopharmacology
Volume	206
Issue number	4
Pages (from-to)	631-40
Number of pages	9
ISSN	0033-3158
DOIs	https://doi.org/10.1007/s00213-009-1540-5 https://doi.org/10.1007/s00213-009-1540-5
Publication status	Published - 2009

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Broberg, B. V., Glenthøj, B. Y., Dias, R., Larsen, D. B., Olsen, C. K., Broberg, B. V., Glenthøj, B. Y., Dias, R., Larsen, D. B., & Olsen, C. K. (2009). Reversal of cognitive deficits by an ampakine (CX516) and sertindole in two animal models of schizophrenia--sub-chronic and early postnatal PCP treatment in attentional set-shifting. Psychopharmacology, 206(4), 631-40. https://doi.org/10.1007/s00213-009-1540-5, https://doi.org/10.1007/s00213-009-1540-5

Reversal of cognitive deficits by an ampakine (CX516) and sertindole in two animal models of schizophrenia--sub-chronic and early postnatal PCP treatment in attentional set-shifting. / Broberg, Brian Villumsen; Glenthøj, Birte Yding; Dias, Rebecca et al.

In: Psychopharmacology, Vol. 206, No. 4, 2009, p. 631-40.

Research output: Contribution to journal › Journal article › Research › peer-review

Broberg, BV, Glenthøj, BY, Dias, R, Larsen, DB, Olsen, CK, Broberg, BV, Glenthøj, BY, Dias, R, Larsen, DB & Olsen, CK 2009, 'Reversal of cognitive deficits by an ampakine (CX516) and sertindole in two animal models of schizophrenia--sub-chronic and early postnatal PCP treatment in attentional set-shifting', Psychopharmacology, vol. 206, no. 4, pp. 631-40. https://doi.org/10.1007/s00213-009-1540-5, https://doi.org/10.1007/s00213-009-1540-5

Broberg BV, Glenthøj BY, Dias R, Larsen DB, Olsen CK, Broberg BV et al. Reversal of cognitive deficits by an ampakine (CX516) and sertindole in two animal models of schizophrenia--sub-chronic and early postnatal PCP treatment in attentional set-shifting. Psychopharmacology. 2009;206(4):631-40. doi: 10.1007/s00213-009-1540-5, http://dx.doi.org/10.1007/s00213-009-1540-5

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title = "Reversal of cognitive deficits by an ampakine (CX516) and sertindole in two animal models of schizophrenia--sub-chronic and early postnatal PCP treatment in attentional set-shifting",

abstract = "RATIONALE: Therapies treating cognitive impairments in schizophrenia especially deficits in executive functioning are not available at present. OBJECTIVE: The current study evaluated the effect of ampakine CX516 in reversing deficits in executive functioning as represented in two animal models of schizophrenia and assessed by a rodent analog of the intradimensional-extradimensional (ID-ED) attentional set-shifting task. The second generation antipsychotic, sertindole, provided further validation of the schizophrenia-like disease models. METHODS: Animals were subjected to (a) sub-chronic or (b) early postnatal phencyclidine (PCP) treatment regimes: (a) Administration of either saline or PCP (5 mg/kg, intraperitonally b.i.d. for 7 days) followed by a 7-day washout period and testing on day 8. (b) On postnatal days (PNDs) 7, 9, and 11, rats were subjected to administration of either saline or PCP (20 mg/kg, subcutaneously (s.c.)) and tested on PNDs 56-95, after reaching adulthood. The single test session required rats to dig for food rewards in a series of discriminations following acute administration of either vehicle, or CX516 (5-40 mg/kg, s.c.), or sertindole (1.25 mg/kg, perorally). RESULTS: The specific extradimensional deficits produced by sub-chronic or early postnatal PCP treatment were significantly attenuated by sertindole and dose-dependently by CX516. CONCLUSION: Findings here further establish PCP treatment as model of executive functioning deficits related to schizophrenia and provide evidence that direct glutamatergic interventions could improve these, when assessed in the ID-ED attentional set-shifting task.",

author = "Broberg, {Brian Villumsen} and Glenth{\o}j, {Birte Yding} and Rebecca Dias and Larsen, {Dorrit Bjerg} and Olsen, {Christina Kurre} and Broberg, {Brian Villumsen} and Glenth{\o}j, {Birte Yding} and Rebecca Dias and Larsen, {Dorrit Bjerg} and Olsen, {Christina Kurre}",

note = "Keywords: Animals; Antipsychotic Agents; Attention; Dioxoles; Disease Models, Animal; Dose-Response Relationship, Drug; Imidazoles; Indoles; Male; Phencyclidine; Piperidines; Rats; Schizophrenia",

year = "2009",

doi = "10.1007/s00213-009-1540-5",

language = "English",

volume = "206",

pages = "631--40",

journal = "Psychopharmacology",

issn = "0033-3158",

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T1 - Reversal of cognitive deficits by an ampakine (CX516) and sertindole in two animal models of schizophrenia--sub-chronic and early postnatal PCP treatment in attentional set-shifting

AU - Broberg, Brian Villumsen

AU - Glenthøj, Birte Yding

AU - Dias, Rebecca

AU - Larsen, Dorrit Bjerg

AU - Olsen, Christina Kurre

AU - Broberg, Brian Villumsen

AU - Glenthøj, Birte Yding

AU - Dias, Rebecca

AU - Larsen, Dorrit Bjerg

AU - Olsen, Christina Kurre

N1 - Keywords: Animals; Antipsychotic Agents; Attention; Dioxoles; Disease Models, Animal; Dose-Response Relationship, Drug; Imidazoles; Indoles; Male; Phencyclidine; Piperidines; Rats; Schizophrenia

PY - 2009

Y1 - 2009

N2 - RATIONALE: Therapies treating cognitive impairments in schizophrenia especially deficits in executive functioning are not available at present. OBJECTIVE: The current study evaluated the effect of ampakine CX516 in reversing deficits in executive functioning as represented in two animal models of schizophrenia and assessed by a rodent analog of the intradimensional-extradimensional (ID-ED) attentional set-shifting task. The second generation antipsychotic, sertindole, provided further validation of the schizophrenia-like disease models. METHODS: Animals were subjected to (a) sub-chronic or (b) early postnatal phencyclidine (PCP) treatment regimes: (a) Administration of either saline or PCP (5 mg/kg, intraperitonally b.i.d. for 7 days) followed by a 7-day washout period and testing on day 8. (b) On postnatal days (PNDs) 7, 9, and 11, rats were subjected to administration of either saline or PCP (20 mg/kg, subcutaneously (s.c.)) and tested on PNDs 56-95, after reaching adulthood. The single test session required rats to dig for food rewards in a series of discriminations following acute administration of either vehicle, or CX516 (5-40 mg/kg, s.c.), or sertindole (1.25 mg/kg, perorally). RESULTS: The specific extradimensional deficits produced by sub-chronic or early postnatal PCP treatment were significantly attenuated by sertindole and dose-dependently by CX516. CONCLUSION: Findings here further establish PCP treatment as model of executive functioning deficits related to schizophrenia and provide evidence that direct glutamatergic interventions could improve these, when assessed in the ID-ED attentional set-shifting task.

AB - RATIONALE: Therapies treating cognitive impairments in schizophrenia especially deficits in executive functioning are not available at present. OBJECTIVE: The current study evaluated the effect of ampakine CX516 in reversing deficits in executive functioning as represented in two animal models of schizophrenia and assessed by a rodent analog of the intradimensional-extradimensional (ID-ED) attentional set-shifting task. The second generation antipsychotic, sertindole, provided further validation of the schizophrenia-like disease models. METHODS: Animals were subjected to (a) sub-chronic or (b) early postnatal phencyclidine (PCP) treatment regimes: (a) Administration of either saline or PCP (5 mg/kg, intraperitonally b.i.d. for 7 days) followed by a 7-day washout period and testing on day 8. (b) On postnatal days (PNDs) 7, 9, and 11, rats were subjected to administration of either saline or PCP (20 mg/kg, subcutaneously (s.c.)) and tested on PNDs 56-95, after reaching adulthood. The single test session required rats to dig for food rewards in a series of discriminations following acute administration of either vehicle, or CX516 (5-40 mg/kg, s.c.), or sertindole (1.25 mg/kg, perorally). RESULTS: The specific extradimensional deficits produced by sub-chronic or early postnatal PCP treatment were significantly attenuated by sertindole and dose-dependently by CX516. CONCLUSION: Findings here further establish PCP treatment as model of executive functioning deficits related to schizophrenia and provide evidence that direct glutamatergic interventions could improve these, when assessed in the ID-ED attentional set-shifting task.

U2 - 10.1007/s00213-009-1540-5

DO - 10.1007/s00213-009-1540-5

M3 - Journal article

C2 - 19390843

SN - 0033-3158

VL - 206

SP - 631

EP - 640

JO - Psychopharmacology

JF - Psychopharmacology

IS - 4

ER -

Reversal of cognitive deficits by an ampakine (CX516) and sertindole in two animal models of schizophrenia--sub-chronic and early postnatal PCP treatment in attentional set-shifting

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