Impact of specific serotonin receptor modulation on behavioral flexibility

Alvarez, Bryan D.; Morales, Cheyenne A.; Amodeo, Dionisio A.

doi:10.1016/j.pbb.2021.173243

Cited by 21 publications

(15 citation statements)

References 69 publications

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“…Moreover, compounds that increase serotonergic transmission, such as antidepressants, are used in neuropsychiatric diseases where cognitive impairments are present and in particular impairment in decision making 23 . 5-HT1A agonists, especially ones acting mostly on post-synaptic receptors, increase behavioural flexibility and facilitate performances 40 . Similarly, anxiolytics may be beneficial in decision making, particularly when the decision is influenced by an emotional component 26 .…”

Section: Discussionmentioning

confidence: 99%

Improved cognitive performance in trace amine-associated receptor 5 (TAAR5) knock-out mice

Maggi

Bon

Gustincich

et al. 2022

Sci Rep

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Trace amine-associated receptors (TAARs) are a family of G protein-coupled receptors present in mammals in the brain and several peripheral organs. Apart from its olfactory role, TAAR5 is expressed in the major limbic brain areas and regulates brain serotonin functions and emotional behaviours. However, most of its functions remain undiscovered. Given the role of serotonin and limbic regions in some aspects of cognition, we used a temporal decision-making task to unveil a possible role of TAAR5 in cognitive processes. We found that TAAR5 knock-out mice showed a generally better performance due to a reduced number of errors and displayed a greater rate of improvement at the task than WT littermates. However, task-related parameters, such as time accuracy and uncertainty have not changed significantly. Overall, we show that TAAR5 modulates specific domains of cognition, highlighting a new role in brain physiology.

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Section: Discussionmentioning

confidence: 99%

Improved cognitive performance in trace amine-associated receptor 5 (TAAR5) knock-out mice

Maggi

Bon

Gustincich

et al. 2022

Sci Rep

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“…These receptors modulate many hormones like oxytocin, prolactin, vasopressin, cortisol, and corticotropin. Serotonin receptors were also responsible for aggression, anxiety, memory, learning, nausea, mood, and sleep [ 71 , 72 ]. Among such antagonists, tropisetron, a fused pyrrole, an indole analog blocks the action of serotonin at 5HT3 receptors, resulting in control of nausea and vomiting induced by chemotherapy and radiotherapy [ 73 , 74 ].…”

Section: Pyrrole and Pyrrolidine Drug Candidatesmentioning

confidence: 99%

Therapeutic potential of pyrrole and pyrrolidine analogs: an update

Basha¹,

Basavarajaiah²,

Shyamsunder³

2022

Mol Divers

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The chemistry of nitrogen-containing heterocyclic compound pyrrole and pyrrolidine has been a versatile field of study for a long time for its diverse biological and medicinal importance . Biomolecules such as chlorophyll, hemoglobin, myoglobin, and cytochrome are naturally occurring metal complexes of pyrrole. These metal complexes play a vital role in a living system like photosynthesis, oxygen carrier, as well storage, and redox cycling reactions. Apart from this, many medicinal drugs are derived from either pyrrole, pyrrolidine, or by its fused analogs. This review mainly focuses on the therapeutic potential of pyrrole, pyrrolidine, and its fused analogs, more specifically anticancer, anti-inflammatory, antiviral, and antituberculosis. Further, this review summarizes more recent reports on the pyrrole, pyrrolidine analogs, and their biological potential. Graphical Abstract

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“…Recently (Baker et al, 2015 ), it was suggested that the MR may also play a critical role in the coordination of communication between the LHb and HPC since the MR receives strong input from the LHb (Quina et al, 2015 ; Metzger et al, 2017 ), the MR has strong projections to a broad extent of the HPC (Azmitia and Segal, 1978 ; Vertes et al, 1999 ) and the MR has been shown to significantly impact HPC-dependent behaviors and theta/ripple oscillations (Vertes and Kocsis, 1997 ; Wang et al, 2015 ) Thus, the MR is strategically situated to at least assist in the transformation of LHb signals to regulate HPC theta in a manner that facilitates response flexibility. Indeed, a link between serotonergic function and response flexibility is often discussed given the numerous studies that report alterations of serotonin receptors or neurotransmitter release results in difficulties performing classic response flexibility tasks such as set-shifting and strategy shifting (excellent reviews include Nilsson et al, 2015 ; Alvarez et al, 2021 ).…”

Section: Lhb and Response Or Choice Flexibilitymentioning

confidence: 99%

“…Such discrepancy in the literature may be attributed to inter-species differences, as well as the reliability of the drug cocktail protocol. Recent evidence has exposed distinct functions of serotonin subtypes as the main culprit (Alvarez et al, 2021 ). Importantly, Morris et al ( 1999 ) showed that selective serotonin depletion causes significant increases in LHb activity, mimicking the neural correlate of depression, compared to other structures.…”

Section: Lhb Contributes To Response Flexibility Along Multiple Times...mentioning

confidence: 99%

Response Flexibility: The Role of the Lateral Habenula

Hones

Mizumori

2022

Front. Behav. Neurosci.

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The ability to make appropriate decisions that result in an optimal outcome is critical for survival. This process involves assessing the environment as well as integrating prior knowledge about the environment with information about one’s current internal state. There are many neural structures that play critical roles in mediating these processes, but it is not yet known how such information coalesces to influence behavioral output. The lateral habenula (LHb) has often been cited as a structure critical for adaptive and flexible responding when environmental contexts and internal state changes. A challenge, however, has been understanding how LHb promotes response flexibility. In this review, we hypothesize that the LHb enables flexible responding following the integration of context memory and internal state information by signaling downstream brainstem structures known to drive hippocampal theta. In this way, animals respond more flexibly in a task situation not because the LHb selects a particular action, but rather because LHb enhances a hippocampal neural state that is often associated with greater attention, arousal, and exploration. In freely navigating animals, these are essential conditions that are needed to discover and implement appropriate alternative choices and behaviors. As a corollary to our hypothesis, we describe short- and intermediate-term functions of the LHb. Finally, we discuss the effects on the behavior of LHb dysfunction in short- and intermediate-timescales, and then suggest that new therapies may act on the LHb to alleviate the behavioral impairments following long-term LHb disruption.

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Impact of specific serotonin receptor modulation on behavioral flexibility

Cited by 21 publications

References 69 publications

Improved cognitive performance in trace amine-associated receptor 5 (TAAR5) knock-out mice

Improved cognitive performance in trace amine-associated receptor 5 (TAAR5) knock-out mice

Therapeutic potential of pyrrole and pyrrolidine analogs: an update

Response Flexibility: The Role of the Lateral Habenula

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