Nazzareno Cannella, Veronica Lunerti, Qianwei Shen, Hongwu Li, Federica Benvenuti, Laura Soverchia, Rajesh Narendran, Friedbert Weiss, Roberto Ciccocioppo
Maintenance therapy with buprenorphine and methadone is the gold standard pharmacological treatment for opioid use disorder (OUD). Despite these compounds demonstrating substantial efficacy, a significant number of patients do not show optimal therapeutic responses. The abuse liability of these medications is also a concern. Here we used rats to explore the therapeutic potential of the new long-acting pan-opioid agonist Cebranopadol in OUD. We tested the effect of cebranopadol on heroin self-administration and yohimbine-induced reinstatement of heroin seeking...
June 18, 2024: Neuropharmacology
Yali Wu, Xinyi Wang, Wenli Zhang, Jun Fu, Kaidong Jiang, Yuying Shen, Chen Li, Hongchang Gao
BACKGROUND: Type 2 diabetes (T2D), a chronic metabolic disease, occurs brain dysfunction accompanied with neuroinflammation and metabolic disorders. The neuroprotective effects of the basic fibroblast growth factor (bFGF) have been well studied. However, the mechanism underlying the anti-inflammatory effects of bFGF remains elusive. METHODS: In this study, db/db mice were employed as an in vivo model, while high glucose (HG)-induced SY5Y cells and LPS-induced BV2 cells were used as in vitro models...
June 18, 2024: Neuropharmacology
Graham L Collingridge, David E Jane
No abstract text is available yet for this article.
June 17, 2024: Neuropharmacology
Carolyn J Stopera, Mitchell J Bartlett, Chenxi Liu, Alexander Esqueda, Raveena Parmar, M Leandro Heien, Scott J Sherman, Torsten Falk
Sub-anesthetic ketamine treatment has been shown to be an effective therapy for treatment-resistant depression and chronic pain. Our group has previously shown that sub-anesthetic ketamine produces acute anti-parkinsonian, and acute anti-dyskinetic effects in preclinical models of Parkinson's disease (PD). Ketamine is a multifunctional drug and exerts effects through blockade of N-methyl-d-aspartate receptors but also through interaction with the opioid system. In this report, we provide detailed pharmacokinetic rodent data on ketamine and its main metabolites following an intraperitoneal injection, and second, we explore the pharmacodynamic properties of ketamine in a rodent PD model with respect to the opioid system, using naloxone, a pan-opioid receptor antagonist, in unilateral 6-hydroxydopamine-lesioned male rats, treated with 6 mg/kg levodopa (l-DOPA) to establish a model of l-DOPA-induced dyskinesia (LID)...
June 16, 2024: Neuropharmacology
Kyung-Jun Boo, Dae Hyun Kim, Eunbi Cho, Dong Hyun Kim, Se Jin Jeon, Chan Young Shin
The endocannabinoid system (ECS) regulates neurotransmission linked to synaptic plasticity, cognition, and emotion. While it has been demonstrated that dysregulation of the ECS in adulthood is relevant not only to central nervous system (CNS) disorders such as autism spectrum disorder, cognitive dysfunction, and depression but also to brain function, there are few studies on how dysregulation of the ECS in the neonatal period affects the manifestation and pathophysiology of CNS disorders later in life. In this study, DO34, a diacylglycerol lipase alpha (DAGLα) inhibitor affecting endocannabinoid 2-AG production, was injected into C57BL/6N male mice from postnatal day (PND) 7 to PND 10, inducing dysregulation of the ECS in the neonatal period...
June 15, 2024: Neuropharmacology
Abbey Myrick, Diane Jimenez, Belkis Jacquez, Melody S Sun, Shahani Noor, Erin D Milligan, C Fernando Valenzuela, David N Linsenbardt
The timing, rate, and quantity of gestational alcohol consumption, collectively referred to here as Maternal Drinking Patterns (MDPs), are of known importance to fetal developmental outcomes. However, few studies have directly evaluated the impact of MDPs on offspring behavior. To do so, we used specialized equipment to record the precise amount and timing of alcohol consumption in pregnant dams, and then characterized MDPs using Principle Component Analysis (PCA). We next tested offspring on behaviors we have previously identified as impacted by prenatal alcohol exposure, and evaluated them where possible in the context of MDPs...
June 13, 2024: Neuropharmacology
Kun Tong, Jing-Wei Zhang, Si-Qi Jing, Xin-Yu Zhao, Jie Han, Yu-Tong Song, Li Yang, Tong Wu, Jing-Ru Hao, Nan Sun, Can Gao
Clinical surgery can lead to severe neuroinflammation and cognitive dysfunctions. It has been reported that astrocytes mediate memory formation and postoperative cognitive dysfunction (POCD), however, the thalamic mechanism of astrocytes in mediating POCD remains unknown. Here, we report that reactive astrocytes in zona incerta (ZI) mediate surgery-induced recognition memory impairment in male mice. Immunostaining results showed that astrocytes are activated with GABA transporter-3 (GAT-3) being down-expressed, and neurons were suppressed in the ZI...
June 13, 2024: Neuropharmacology
Yuri A Blednov, William Shawlot, Gregg E Homanics, Elizabeth A Osterndorff-Kahanek, Sonia Mason, Jody Mayfield, Joshua L Smalley, Stephen J Moss, Robert O Messing
We previously showed that the PDE4 inhibitor apremilast reduces ethanol consumption in mice by protein kinase A (PKA) and GABAergic mechanisms. Preventing PKA phosphorylation of GABAA β3 subunits partially blocked apremilast-mediated decreases in drinking. Here, we produced Gabrb1-S409A mice to render GABAA β1 subunits resistant to PKA-mediated phosphorylation. Mass spectrometry confirmed the presence of the S409A mutation and lack of changes in β1 subunit expression or phosphorylation at other residues...
June 12, 2024: Neuropharmacology
Filomene G Morrison, Lori Jean Van Orden, Karla Zeitz, Eloise J Kuijer, Sharon L Smith, David J Heal, Tanya L Wallace
Kappa opioid receptors (KORs) are implicated in the pathophysiology of various psychiatric and neurological disorders creating interest in targeting the KOR system for therapeutic purposes. Accordingly, navacaprant (NMRA-140) is a potent, selective KOR antagonist being evaluated as a treatment for major depressive disorder. In the present report, we have extended the pharmacological characterization of navacaprant by further demonstrating its selective KOR antagonist properties and confirming its lack of agonist activity at KORs and related targets involved in opioid-related abuse...
June 12, 2024: Neuropharmacology
Guilherme Shigueto Vilar Higa, Felipe José Costa Viana, José Francis-Oliveira, Emily Cruvinel, Thainá Soares Franchin, Tania Marcourakis, Henning Ulrich, Roberto De Pasquale
Synaptic plasticity constitutes a fundamental process in the reorganization of neural networks that underlie memory, cognition, emotional responses, and behavioral planning. At the core of this phenomenon lie Hebbian mechanisms, wherein frequent synaptic stimulation induces long-term potentiation (LTP), while less activation leads to long-term depression (LTD). The synaptic reorganization of neuronal networks is regulated by serotonin (5-HT), a neuromodulator capable of modify synaptic plasticity to appropriately respond to mental and behavioral states, such as alertness, attention, concentration, motivation, and mood...
June 12, 2024: Neuropharmacology
Eric J Nunes, Nardos Kebede, Anjali M Rajadhyaksha, Nii A Addy
Exposure to chronic and unpredictable stressors can precipitate mood-related disorders in humans, particularly in individuals with pre-existing mental health challenges. L-type calcium channels (LTCCs) have been implicated in numerous neuropsychiatric disorders, as LTCC encoding genes have been identified as candidate risk factors for neuropsychiatric illnesses. In these sets of experiments, we sought to examine the ability of LTCC blockade to alter depression, anxiety, and anhedonic-related behavioral responses to chronic unpredictable stress (CUS) exposure in female and male rats...
June 11, 2024: Neuropharmacology
Ruotong Li, Yaxin Yang, Ling Wang, Guoyi Tang, Jie Yang, Shasha Gao, Jian Liu
The anteroventral bed nucleus of stria terminalis (avBNST) is a limbic forebrain region involved in the regulation of anxiety, and expresses GABAB receptors, which are located at both pre- and post-synaptic sites. However, it is unclear how blockade of these receptors affects anxiety-like behaviors, particularly in Parkinson's disease (PD)-related anxiety. In the present study, unilateral 6-hydroxydopamine (6-OHDA) lesions of the substantia nigra pars compacta in rats induced anxiety-like behaviors, and increased GABA release and decreased glutamate release in the avBNST, as well as decreased level of dopamine (DA) in the basolateral amygdala (BLA)...
June 10, 2024: Neuropharmacology
Yue Zhou, Wei Dong, Yong-Kang Qiu, Ke-Jie Shao, Zi-Xin Zhang, Jia-Qi Yao, Tian-Qi Chen, Zi-Yi Li, Chen-Rui Zhou, Xin-Hao Jiao, Yu Chen, Han Lu, Yu-Qing Wu
The full mechanism of action of propofol, a commonly administered intravenous anesthetic drug in clinical practice, remains elusive. The focus of this study was the role of GABAergic neurons which are the main neuron group in the ventral pallidum (VP) closely associated with anesthetic effects in propofol anesthesia. The activity of VP GABAergic neurons following propofol anesthesia in Vgat-Cre mice was observed via detecting c-Fos immunoreactivity by immunofluorescence and western blotting. Subsequently, chemogenetic techniques were employed in Vgat-Cre mice to regulate the activity of VP GABAergic neurons...
June 7, 2024: Neuropharmacology
Han Jiao, Andries Kalsbeek, Chun-Xia Yi
Microglia, a vital homeostasis-keeper of the central nervous system, perform critical functions such as synaptic pruning, clearance of cellular debris, and participation in neuroinflammatory processes. Recent research has shown that microglia exhibit strong circadian rhythms that not only actively regulate their own immune activity, but also affect neuronal function. Disruptions of the circadian clock have been linked to a higher risk of developing a variety of diseases. In this article we will provide an overview of how lifestyle factors impact microglial function, with a focus on disruptions caused by irregular sleep-wake patterns, reduced physical activity, and eating at the wrong time-of-day...
June 7, 2024: Neuropharmacology
Randall J Olson, Lowell Bartlett, Alex Sonneborn, Russell Milton, Zachary Bretton-Granatoor, Ayesha Firdous, Alexander Z Harris, Atheir I Abbas
Administration or consumption of classic psychedelics (CPs) leads to profound changes in experience which are often described as highly novel and meaningful. They have shown substantial promise in treating depressive symptoms and may be therapeutic in other situations. Although research suggests that the therapeutic response is correlated with the intensity of the experience, the neural circuit basis for the alterations in experience caused by CPs requires further study. The medial prefrontal cortex (mPFC), where CPs have been shown to induce rapid, 5-HT2A receptor-dependent structural and neurophysiological changes, is believed to be a key site of action...
June 6, 2024: Neuropharmacology
Aki Takahashi
There is an important relationship between the immune system and aggressive behavior. Aggressive encounters acutely increase the levels of proinflammatory cytokines, and there are positive correlations between aggressive traits and peripheral proinflammatory cytokines. Endotoxin lipopolysaccharide (LPS) treatment, which results in peripheral immune activation, decreases aggressive behavior as one of the sickness behavioral symptoms. In contrast, certain brain infections and chronic interferon treatment are associated with increased aggression...
May 31, 2024: Neuropharmacology
Jessica Santollo, Derek Daniels
Water is critical for survival and thirst is a powerful way of ensuring that fluid levels remain in balance. Overconsumption, however, can have deleterious effects, therefore optimization requires a need to balance the drive for water with the satiation of that water drive. This review will highlight our current understanding of how thirst is both generated and quenched, with particular focus on the roles of angiotensin II, glucagon like-peptide 1, and estradiol in turning on and off the thirst drive. Our understanding of the roles these bioregulators play has benefited from modern behavioral analyses, which have improved the time resolution of intake measures, allowing for attention to the details of the patterns within a bout of intake...
May 30, 2024: Neuropharmacology
Jennifer Pocock, Foteini Vasilopoulou, Elina Svensson, Katharina Cosker
TREM2 is a membrane receptor solely expressed on microglia in normal brain. In this review we outline recent advances in TREM2 biology and its implications for microglial function, with particular emphasis on findings from iPSC-derived microglia (iMG) expressing TREM2 loss-of-function mutations. Alterations in receptor proximal and distal signalling underlie TREM2 risk variants linked to neurodegenerative disease, principally NH-linked FTD, and late-onset AD, but emerging data suggest roles for TREM2 in PD, MS and ALS...
May 29, 2024: Neuropharmacology
Cambria R Beane, Delainey G Lewis, Nicolaus Bruns Vi, Kat L Pikus, Mary H Durfee, Roman A Zegarelli, Thomas W Perry, Oscar Sandoval, Anna K Radke
The endogenous opioid system has been implicated in alcohol consumption and preference in both humans and animals. The mu opioid receptor (MOR) is expressed on multiple cells in the striatum, however little is known about the contributions of specific MOR populations to alcohol drinking behaviors. The current study used mice with a genetic deletion of MOR in cholinergic cells (ChAT-Cre/Oprm1fl/fl ) to examine the role of MORs expressed in cholinergic interneurons (CINs) in home cage self-administration paradigms...
May 27, 2024: Neuropharmacology
Simone Larsen Bærentzen, Majken Borup Thomsen, Aage Ko Alstrup, Gregers Wegener, David J Brooks, Michael Winterdahl, Anne M Landau
Diets high in sucrose and fat are becoming more prevalent the world over, accompanied by a raised prevalence of cardiovascular diseases, cancers, diabetes, obesity, and metabolic syndrome. Clinical studies link unhealthy diets with the development of mental health disorders, particularly depression. Here, we investigate the effects of 12 days of sucrose consumption administered as two liters of 25% sucrose solution daily for 12 days in Göttingen minipigs on the function of brain receptors involved in reward and motivation, regulating feeding, and pre- and post-synaptic mechanisms...
May 27, 2024: Neuropharmacology
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