Targeting dopamine transporter to ameliorate cognitive deficits in Alzheimer's disease

Shaikh, Ammara; Ahmad, Fairus; Teoh, Seong Lin; Kumar, Jaya; Yahaya, Mohamad Fairuz

doi:10.3389/fncel.2023.1292858

Cited by 6 publications

(1 citation statement)

References 102 publications

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“…Dopamine elevation in the brain has been suggested as an alternative to ameliorate cognitive deficits observed in Alzheimer's disease ( Ambree et al, 2009 ; Shaikh et al, 2023 ). However, in the context of Parkinson's disease it is known that the global elevation of dopamine in the brain by the use of dopaminergic agonists produces nondesired side effects such as ʟ-DOPA induced dyskinesias, hallucinations, and compulsive behaviors ( Talati et al, 2009 ; Voon et al, 2011 ; Blandini and Armentero, 2014 ), highlighting the need of pharmacological tools that allow the temporal and spatial control of dopamine release.…”

Section: Introductionmentioning

confidence: 99%

Paradoxical Boosting of Weak and Strong Spatial Memories by Hippocampal Dopamine Uncaging

Velazquez-Delgado,

Perez-Becerra,

Calderon

et al. 2024

eNeuro

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The ability to remember changes in the surroundings is fundamental for daily life. It has been proposed that novel events producing dopamine release in the hippocampal CA1 region could modulate spatial memory formation. However, the role of hippocampal dopamine increase on weak or strong spatial memories remains unclear. We show that male mice exploring two objects located in a familiar environment for 5 minutes created a short-term memory (weak) that cannot be retrieved one day later, whereas 10 minutes exploration created a long-term memory (strong) that can be retrieved one day later. Remarkably, hippocampal dopamine elevation during the encoding of weak object location memories (OLMs) allowed their retrieval one day later but dopamine elevation during the encoding of strong OLMs promoted the preference for a familiar object location over a novel object location after 24 hours. Moreover, dopamine uncaging after the encoding of OLMs did not have effect on weak memories whereas on strong memories diminished the exploration of the novel object location. Additionally, hippocampal dopamine elevation during the retrieval of OLMs did not allow the recovery of weak memories and did not affect the retrieval of strong memory traces. Finally, dopamine elevation increased hippocampal theta oscillations, indicating that dopamine promotes the recurrent activation of specific groups of neurons. Our experiments demonstrate that hippocampal dopaminergic modulation during the encoding of OLMs depends on memory strength indicating that hyperdopaminergic levels that enhance weak experiences could compromise the normal storage of strong memories.Significance statementIncreased levels of dopamine have been related to cognitive enhancement. Hippocampal dopamine elevation caused by novelty exposure has been proposed as a strategy to enhance memory based on the observation that surprising events create flashbulb memories that are remembered for long time. However, hyperdopaminergic levels could also underlie maladaptive memories, such as non-desired preservation of traumatic experiences. Our experiments show that dopamine elevation in the dorsal hippocampus during the encoding of spatial memories has paradoxical effects, while the enhancement of weak memories allows their retrieval, the dopaminergic modulation of strong memories limits the ability to modify preexisting spatial memories by changes in the environment. We conclude that cognitive enhancement through dopamine boosting must consider diverse aspects of memory formation.

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