The neuropharmacological properties of α‐pyrrolidinobutiothiophenone, a new synthetic cathinone, in rodents; role of the dopaminergic system DOI
Oc‐Hee Kim,

Kyung Oh Jeon,

Gihyeon Kim

и другие.

British Journal of Pharmacology, Год журнала: 2024, Номер 181(18), С. 3462 - 3482

Опубликована: Май 21, 2024

Abstract Background and Purpose α‐Pyrrolidinobutiothiophenone (α‐PBT) is a chemical derivative of cathinone, structural analogue amphetamine. Until now, there have been few previous neurochemical or neurobehavioural studies on the abuse potential α‐PBT. Experimental Approach We examined α‐PBT by measuring psychomotor, rewarding, reinforcing properties methamphetamine‐like discriminative stimulus effects in rodents using locomotor activity, conditioned place preference, self‐administration, drug discrimination studies. To clarify underlying neuropharmacological mechanisms, we measured dopamine levels neuronal activation dorsal striatum. In addition, investigated role D 1 receptor 2 receptors α‐PBT‐induced hyperlocomotor effect rodents. Key Results promoted activity mice. induced drug‐paired preference mice supported self‐administration rats. experiment, fully substituted for methamphetamine Furthermore, increased c‐Fos expression striatum mice, which was associated with these behaviours. Finally, pretreatment antagonist SCH23390 eticlopride significantly attenuated acute repeated Conclusions Implications These findings suggest that has at highest dose tested via enhanced dopaminergic transmission The results provide scientific evidence legal restrictions recreational use

Язык: Английский

Cholecystokinin (CCK): a neuromodulator with therapeutic potential in Alzheimer’s and Parkinson’s disease DOI Creative Commons
Niklas Reich, Christian Hölscher

Frontiers in Neuroendocrinology, Год журнала: 2024, Номер 73, С. 101122 - 101122

Опубликована: Фев. 11, 2024

Cholecystokinin (CCK) is a neuropeptide modulating digestion, glucose levels, neurotransmitters and memory. Recent studies suggest that CCK exhibits neuroprotective effects in Alzheimer's disease (AD) Parkinson's (PD). Thus, we review the physiological function therapeutic potential of CCK. The facilitates hippocampal glutamate release gates GABAergic basket cell activity, which improves declarative memory acquisition, but inhibits consolidation. Cortical alters recognition enhances audio-visual processing. By stimulating CCK-1 receptors (CCK-1Rs), sulphated CCK-8 elicits dopamine substantia nigra striatum. In mesolimbic pathway, triggered by terminates reward responses via CCK-2Rs. Importantly, activation nigral CCK-2Rs evoking AMPK activation, expression mitochondrial fusion modulators autophagy. Other benefits include vagus nerve/CCK-1R-mediated brain-derived neurotrophic factor, intestinal protection suppression inflammation. We also discuss caveats combination with other peptide hormones.

Язык: Английский

Процитировано

18
Dopamine D1–D5 Receptors in Brain Nuclei: Implications for Health and Disease DOI Creative Commons
K. Kawahata, David I. Finkelstein, Kohji Fukunaga

и другие.

Receptors, Год журнала: 2024, Номер 3(2), С. 155 - 181

Опубликована: Апрель 12, 2024

Understanding the intricate role of dopamine D1–D5 receptors is pivotal in addressing challenges posed by aging global population, as well social stress and advancing therapeutic interventions. Central to diverse brain functions such movement, cognition, motivation, reward, are ubiquitously distributed across various nuclei. This comprehensive review explores nuanced each receptor, D1, D2, D3, D4, D5, distinct regions, elucidating alterations witnessed several neurological psychiatric disorders. From substantia nigra ventral tegmental area, crucial for motor control reward processing, limbic system influencing emotional responses, cognitive functions, nucleus reveals a specific involvement receptors. In addition, genetic variations affect risk developing schizophrenia parkinsonism. The further investigates physiological significance pathogenic impacts critical areas like prefrontal cortex, hypothalamus, striatum. By unraveling complexities receptor biology, especially those focused on different nuclei, this provides foundation understanding their varied roles health disease, which essential development targeted strategies aimed at mitigating impact mental well-being.

Язык: Английский

Процитировано

16
Cell-type-specific optogenetic stimulation of the locus coeruleus induces slow-onset potentiation and enhances everyday memory in rats DOI Creative Commons
Dorothy Tse, Lucia Privitera,

Anna C. Norton

и другие.

Proceedings of the National Academy of Sciences, Год журнала: 2023, Номер 120(46)

Опубликована: Ноя. 6, 2023

Memory formation is typically divided into phases associated with encoding, storage, consolidation, and retrieval. The neural determinants of these are thought to differ. This study first investigated the impact experience novelty in rats incurred at a different time, before or after, precise moment memory encoding. retention was enhanced. Optogenetic activation locus coeruleus mimicked this enhancement induced by novelty, both when given after also slow-onset potentiation field potentials area CA1 hippocampus evoked CA3 stimulation. Despite being considered primarily noradrenergic area, effects such stimulation were blocked dopamine D1/D5 receptor antagonist SCH 23390. These findings substantiate enrich evidence implicating cellular aspects consolidation hippocampus.

Язык: Английский

Процитировано

17
A Cre-dependent reporter mouse for quantitative real-time imaging of protein kinase A activity dynamics DOI Creative Commons

Elizabeth I. Tilden,

Aditi Maduskar,

Anna Oldenborg

и другие.

Scientific Reports, Год журнала: 2024, Номер 14(1)

Опубликована: Фев. 6, 2024

Intracellular signaling dynamics play a crucial role in cell function. Protein kinase A (PKA) is key molecule that has diverse functions, from regulating metabolism and brain activity to guiding development cancer progression. We previously developed an optical reporter, FLIM-AKAR, allows for quantitative imaging of PKA via fluorescence lifetime microscopy photometry. However, using viral infection or electroporation the delivery FLIM-AKAR invasive results variable expression. Here, we reporter mouse, FL-AK, which expresses Cre-dependent manner ROSA26 locus. FL-AK provides robust consistent expression over time. Functionally, mouse line reports increase response activation both G

Язык: Английский

Процитировано

6
Progress on the development of Class A GPCR‐biased ligands DOI Creative Commons
Paula Morales, Magdalena M. Scharf, Marcel Bermúdez

и другие.

British Journal of Pharmacology, Год журнала: 2024, Номер unknown

Опубликована: Сен. 11, 2024

Class A G protein‐coupled receptors (GPCRs) continue to garner interest for their essential roles in cell signalling and importance as drug targets. Although numerous drugs the clinic target these receptors, over 60% GPCRs remain unexploited. Moreover, adverse effects triggered by available unbiased GPCR modulators, limit use therapeutic value. In this context, elucidation of biased has opened up new pharmacological avenues holding promise safer therapeutics. Functionally selective ligands favour receptor conformations facilitating recruitment specific effectors modulation associated pathways. This review surveys current discovery landscape GPCR‐biased modulators with a focus on recent advances. Understanding biological preferential coupling is at different stages depending family. Therefore, individual families, we present compilation functionally reported past few years. doing so, dissect relevance, molecular determinants potential clinical applications.

Язык: Английский

Процитировано

6
Assessment of the relationship between the dopaminergic pathway and severe acute respiratory syndrome coronavirus 2 infection, with related neuropathological features, and potential therapeutic approaches in COVID‐19 infection DOI
Yousef Rasmi,

Ameneh Shokati,

Shima Hatamkhani

и другие.

Reviews in Medical Virology, Год журнала: 2024, Номер 34(1)

Опубликована: Янв. 1, 2024

Dopamine is a known catecholamine neurotransmitter involved in several physiological processes, including motor control, motivation, reward, cognition, and immune function. receptors are widely distributed throughout the nervous system cells. Several viruses, human immunodeficiency virus Japanese encephalitis virus, can use dopaminergic to replicate viral neuropathogenesis. In addition, studies suggest that may play role progression pathogenesis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. When SARS-CoV-2 binds angiotensin-converting enzyme on surface neuronal cells, spike protein bind neighbouring cells accelerate its life cycle exacerbate neurological symptoms. recent research has shown dopamine an important regulator immune-neuroendocrine system. Most express other dopamine-related proteins, indicating importance regulation. The increase concentration during SARS-CoV2 infection reduce immunity (innate adaptive) promotes spread, which could lead damage. signalling be affected by COVID -19 cause various symptoms as it interacts with One possible treatment strategy for patients antagonists. To fully understand how protect from we need study pathophysiology

Язык: Английский

Процитировано

3
Simultaneous activation of different subtypes of dopamine receptors may lead to activation of homeostatic sleep regulatory mechanisms DOI Creative Commons

Dóra Keserű,

Tünde Hajnik,

Máté Pethő

и другие.

Pharmacology Biochemistry and Behavior, Год журнала: 2025, Номер unknown, С. 173954 - 173954

Опубликована: Янв. 1, 2025

Язык: Английский

Процитировано

0
Endogenous Regulator of G protein Signaling 14 (RGS14) blunts cocaine-induced emotionally motivated behaviors in female mice DOI Creative Commons
Sara N. Bramlett, Stephanie L. Foster, David Weinshenker

и другие.

Addiction Neuroscience, Год журнала: 2025, Номер unknown, С. 100203 - 100203

Опубликована: Фев. 1, 2025

Язык: Английский

Процитировано

0
Principles and Design of Molecular Tools for Sensing and Perturbing Cell Surface Receptor Activity DOI
Jennifer Sescil, Steven M. Havens, Wenjing Wang

и другие.

Chemical Reviews, Год журнала: 2025, Номер unknown

Опубликована: Фев. 25, 2025

Cell-surface receptors are vital for controlling numerous cellular processes with their dysregulation being linked to disease states. Therefore, it is necessary develop tools study and the signaling pathways they control. This Review broadly describes molecular approaches that enable 1) visualization of determine localization distribution; 2) sensing receptor activation permanent readouts as well in real time; 3) perturbing activity mimicking receptor-controlled learn more about these processes. Together, have provided valuable insight into fundamental biology helped characterize therapeutics target receptors.

Язык: Английский

Процитировано

0
Neurotransmitters and Receptors: Overview of Targets and Organophosphates as Exemplar Toxicological Insults DOI

Reeya Tanwar,

Jason R. Cannon

Elsevier eBooks, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

Язык: Английский

Процитировано

0