Hippocampal and prefrontal cortical NMDA receptors mediate the interactive effects of olanzapine and lithium in memory retention in rats: the involvement of CAMKII-CREB signaling pathways.
Rationale: Treatment of bipolar disorder (BPD) with lithium and olanzapine concurrent administration is a major medicine issue with the elusive neurobiological mechanisms underlying the cognitive function. Objective: To clarify the precise mechanisms involved, the possible role of the hippocampus (H...
| Publicado en: | Psychopharmacology Vol. 237; no. 5; pp. 1383 - 1397 |
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| Autores principales: | , , , , , |
| Formato: | Journal Article |
| Publicado: |
Springer Nature
May2020
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=142999677&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 142999677 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00333158 EJD jtl: Psychopharmacology issn: 00333158 maglogo: N pubinfo: dt: May2020 vid: 237 iid: 5 pid: 237 pub: Springer Nature place: New York, New York artinfo: ui: 142999677 10.1007/s00213-020-05465-4 142999677 ppf: 1383 ppct: 14 formats: fmt: – @attributes: type: T – @attributes: type: P tig: atl: Hippocampal and prefrontal cortical NMDA receptors mediate the interactive effects of olanzapine and lithium in memory retention in rats: the involvement of CAMKII-CREB signaling pathways. aug: au: Amiri, Shiva Jafari-Sabet, Majid Keyhanfar, Fariborz Falak, Reza Shabani, Mohammad Rezayof, Ameneh affil: Department of Pharmacology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran sug: ab: Rationale: Treatment of bipolar disorder (BPD) with lithium and olanzapine concurrent administration is a major medicine issue with the elusive neurobiological mechanisms underlying the cognitive function. Objective: To clarify the precise mechanisms involved, the possible role of the hippocampus (HPC) and prefrontal cortical (PFC) NMDA receptors and CAMKII-CREB signaling pathway in the interactive effects of lithium and olanzapine in memory consolidation was evaluated. The dorsal hippocampal CA1 regions of adult male Wistar rats were bilaterally cannulated and a step-through inhibitory avoidance apparatus was used to assess memory consolidation. The changes in p-CAMKII/CAMKII and p-CREB/CREB ratio in the HPC and the PFC were measured by Western blot analysis. Results: Post-training administration of lithium (20, 30, and 40 mg/kg, i.p.) dose-dependently decreased memory consolidation whereas post-training administration olanzapine (2 and 5 mg/kg, i.p.) increased memory consolidation. Post-training administration of certain doses of olanzapine (1, 2, and 5 mg/kg, i.p.) dose-dependently improved lithium-induced memory impairment. Post-training administration of ineffective doses of the NMDA (10−5 and 10−4 μg/rat, intra-CA1) plus an ineffective dose of olanzapine (1 mg/kg, i.p.) dose-dependently improved the lithium-induced memory impairment. Post-training microinjection of ineffective doses of the NMDA (10−5 and 10−4 μg/rat, intra-CA1) dose-dependently potentiated the memory improvement induced by olanzapine (1 mg/kg, i.p.) on lithium-induced memory impairment which was associated with the enhancement of the levels of p-CAMKII and p-CREB in the HPC and the PFC. Post-training microinjection of ineffective doses of the noncompetitive NMDA receptor antagonist, MK-801 (0.0625 and 0.0125 μg/rat, intra-CA1), dose-dependently decreased the memory improvement induced by olanzapine (5 mg/kg, i.p.) on lithium-induced memory impairment which was related to the reduced levels of HPC and PFC CAMKII-CREB. Conclusion: The results strongly revealed that there is a functional interaction among lithium and olanzapine through the HPC and the PFC NMDA receptor mechanism in memory consolidation which is mediated with the CAMKII-CREB signaling pathway. pubtype: Academic Journal doctype: Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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