2. Academic Validation
  3. Potentiation of cognitive enhancer effects of Alzheimer's disease medication memantine by alpha7 nicotinic acetylcholine receptor agonist PHA-543613 in the Morris water maze task

Potentiation of cognitive enhancer effects of Alzheimer's disease medication memantine by alpha7 nicotinic acetylcholine receptor agonist PHA-543613 in the Morris water maze task

  • Psychopharmacology (Berl). 2021 Nov;238(11):3273-3281. doi: 10.1007/s00213-021-05942-4.
Nóra Bruszt 1 2,  Zsolt Kristóf Bali 3 4 5,  Sai Ambika Tadepalli 1 6,  Lili Veronika Nagy 1 6,  István Hernádi 1 2 7 6
Affiliations

Affiliations

  • 1 János Szentágothai Research Center, Center for Neuroscience, University of Pécs, 20 Ifjúság str, 7624, Pécs, Hungary.
  • 2 Institute of Physiology, Medical School, University of Pécs, 12 Szigeti str, 7624, Pécs, Hungary.
  • 3 János Szentágothai Research Center, Center for Neuroscience, University of Pécs, 20 Ifjúság str, 7624, Pécs, Hungary. [email protected].
  • 4 Institute of Physiology, Medical School, University of Pécs, 12 Szigeti str, 7624, Pécs, Hungary. [email protected].
  • 5 Grastyán Endre Translational Research Center, University of Pécs, 6 Ifjúság str, 7624, Pécs, Hungary. [email protected].
  • 6 Department of Experimental Zoology and Neurobiology, Faculty of Sciences, University of Pécs, 6 Ifjúság str, 7624, Pécs, Hungary.
  • 7 Grastyán Endre Translational Research Center, University of Pécs, 6 Ifjúság str, 7624, Pécs, Hungary.
PMID: 34387707 DOI: 10.1007/s00213-021-05942-4
Abstract

Rationale: There are controversial pieces of evidence whether combination therapies using memantine and cholinesterase inhibitors are beneficial over their monotreatments. However, results of preclinical studies are promising when memantine is combined with agonists and allosteric modulators of the alpha7 nicotinic acetylcholine receptor (nAChR).

Objectives: Here, we tested the hypothesis that cognitive enhancer effects of memantine can be potentiated through modulating alpha7 nAChRs in a scopolamine-induced amnesia model.

Methods: Monotreatments, as well as co-administrations of selective alpha7 nicotinic acetylcholine receptor agonist PHA-543613 and memantine were tested in the Morris water maze task in rats. The efficacy of the co-administration treatment was observed on different domains of spatial episodic memory.

Results: Low dose of memantine (0.1 mg/kg) and PHA-543613 (0.3 mg/kg) successfully reversed scopolamine-induced short-term memory deficits both in monotreatments and in co-administration. When recall of information from long-term memory was tested, pharmacological effects caused by co-administration of subeffective doses of memantine and PHA-543613 exceeded that of their monotreatments.

Conclusion: Our results further support the evidence of beneficial interactions between memantine and alpha7 nAChR ligands and suggest a prominent role of alpha7 nAChRs in the procognitive effects of memantine.

Keywords

Behavior; Combined treatment; Dementia; Long-term memory; Scopolamine; Spatial learning.

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