Review
Pharmacology & Pharmacy
Emily R. Trunnell, Constanca Carvalho
Summary: Despite the prevalence of treatment-resistant depression, many pharmaceutical companies have abandoned the development of new antidepressants due to low quality preclinical tests, such as over-reliance on animal behavioral screens like the forced swim test (FST). A retrospective review found that out of 109 compounds tested in the FST, only 28% were explored for antidepressant effects in humans, and only three showed potential efficacy, but are not approved for treating depression. This suggests that the FST may not be a useful screening tool for identifying novel antidepressants.
DRUG DISCOVERY TODAY
(2021)
Review
Neurosciences
Marc L. Molendijk, E. Ronald de Kloet
Summary: The immobility response in the forced swim test is not considered a rodent model of depression, but it can predict a compound's antidepressant potential to some extent. Despite some papers labeling immobility as depression-like behavior, the perspective on this issue varies among different countries.
EUROPEAN JOURNAL OF NEUROSCIENCE
(2022)
Review
Pharmacology & Pharmacy
Christiane Brandwein, Cathalijn H. C. Leenaars, Laura Becker, Natascha Pfeiffer, Ana -Maria Iorgu, Melissa Hahn, Gaia A. Vairani, Lars Lewejohann, Andre Bleich, Anne S. Mallien, Peter Gass
Summary: This systematic mapping review provides a comprehensive overview of the evolution and commonly used set-ups of the Porsolt Forced Swim Test in rats. By offering detailed technical aspects and a list of existing publications, it enhances the reproducibility and comparability of this experiment, aiming to reduce animal usage and unnecessary replication.
PHARMACOLOGICAL RESEARCH
(2023)
Article
Pharmacology & Pharmacy
Mohammed H. Elkomy, Fatma I. Abo El-Ela, Randa Mohammed Zaki, Omar A. Alsaidan, Mohammed Elmowafy, Ameeduzzafar Zafar, Khaled Shalaby, Mohamed A. Abdelgawad, Hany A. Omar, Rania Salama, Hussein M. Eid
Summary: This study developed and optimized a drug-loaded thermosensitive gel for intranasal administration to combat depression. The results demonstrated that compared to other formulations, this thermosensitive gel significantly improved behavioral performance and alleviated neural tissue changes in depressed rats. Further research is needed to determine its effectiveness in humans.
Article
Biochemistry & Molecular Biology
Sebastien Bullich, Sarah Delcourte, Nasser Haddjeri, Bruno P. Guiard
Summary: The study found that 5d-RFSS mice exhibited strong depressive characteristics in the FST, but the model has limitations in replicating the broad spectrum of depressive symptoms observed in other chronic models. However, it showed a significant impact on the hypothalamic-pituitary-adrenal axis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Neurosciences
Elena Carazo-Arias, Phi T. Nguyen, Marley Kass, Hyun Jung Jee, Katherine M. Nautiyal, Valerie Magalong, Lilian Coie, Valentine Andreu, Mark M. Gergues, Huzefa Khalil, Huda Akil, Danusa Mar Arcego, Michael Meaney, Christoph Anacker, Benjamin A. Samuels, John E. Pintar, Irina Morozova, Sergey Kalachikov, Rene Hen
Summary: The opioid system is involved in the antidepressant effects of fluoxetine, potentially mediated through the upregulation of proenkephalin in a specific subgroup of mature granule cells.
BIOLOGICAL PSYCHIATRY
(2022)
Article
Psychiatry
Sandra Ledesma-Corvi, Elena Hernandez-Hernandez, M. Julia Garcia-Fuster
Summary: There is an urgent need to develop new pharmacological treatments for adolescent depression, with inclusion of sex as a biological variable in preclinical studies. This study compared ketamine and cannabidiol with fluoxetine in adolescent rats exposed to early-life stress, incorporating a sex perspective. The main findings indicated an antidepressant-like potential for ketamine and cannabidiol in adolescent rats, dependent on sex, stress exposure, treatment length, and behavioral features. Male rats showed improvement in affective-like features with all tested antidepressants, while female rats were mostly unresponsive. Re-exposure to the same drug regimens in adulthood resulted in decreased efficacy. Further characterization of the long-term safety and effects for both sexes is needed before ketamine or cannabidiol can be considered as antidepressants for adolescents.
TRANSLATIONAL PSYCHIATRY
(2022)
Article
Neurosciences
Josh Allen, Raquel Romay-Tallon, Milann A. Mitchell, Kyle J. Brymer, Jenessa Johnston, Carla L. Sanchez-Lafuente, Graziano Pinna, Lisa E. Kalynchuk, Hector J. Caruncho
Summary: Chronic stress is a significant risk factor for depression. Reelin protein can rapidly restore depressive-like behavior and neurochemical abnormalities induced by chronic stress through intravenous injections.
Article
Neurosciences
Benjamin Aliphon, Twain Dai, Jessica Moretti, Marissa Penrose-Menz, Wilhelmina H. A. M. Mulders, Dominique Blache, Jennifer Rodger
Summary: This study validated a repeated measures cognitive affective bias (CAB) test in a rat model of chronic stress and compared it with the forced swim test (FST). The results showed that the CAB test can be used as a behavioral testing method for assessing affective disorders.
PSYCHOPHARMACOLOGY
(2023)
Article
Education, Scientific Disciplines
Manish Bansilal Gagarani, Prakash Hiraman Patil
Summary: This study confirms the significant antidepressant effect of chloroform and ethyl acetate fractions of Cassine albens, indicating its potential clinical application for treating depression symptoms in olfactory bulbectomized mice.
INDIAN JOURNAL OF PHARMACEUTICAL EDUCATION AND RESEARCH
(2022)
Article
Neurosciences
A. G. Sartim, J. Marques, K. M. Silveira, P. H. Gobira, F. S. Guimaraes, G. Wegener, S. R. Joca
Summary: The study found that CBD can exhibit antidepressant effects without causing hyperactivity, and it can also inhibit the psychostimulant effects induced by ketamine. The combined administration of CBD and ketamine may be a promising therapeutic strategy for achieving antidepressant effects while reducing unwanted side effects.
Article
Behavioral Sciences
Mareli Roets, Linda Brand, Stephan F. Steyn
Summary: During the peripartum period, women are at an increased risk of developing perinatal distress. Animal studies have shown that pregnancy can alter the bio-behavioural profile of rats, and postpartum stressors can exacerbate these effects. These findings suggest that pregnancy influences postpartum behaviour in a strain-dependent manner.
BEHAVIOURAL BRAIN RESEARCH
(2023)
Article
Behavioral Sciences
Kyle J. Brymer, Erin Y. Kulhaway, John G. Howland, Hector J. Caruncho, Lisa E. Kalynchuk
Summary: Repeated corticosterone injections in rats lead to cognitive deficits and depression-like behavior, highlighting the importance of considering cognitive impairments in assessing depression. Corticosterone significantly affects body weight, immobility in the forced swim test, startle amplitudes, and object recognition memory, suggesting a complex phenotype induced by chronic stress.
BEHAVIOURAL BRAIN RESEARCH
(2021)
Article
Plant Sciences
Taiwo G. Olubodun-Obadun, Ismail O. Ishola, Timisola P. Adesokan, Blessing O. Anih, Olufunmilayo O. Adeyemi
Summary: This study investigates the antidepressant and anxiolytic effects of ethanol seed extract of Cajanus cajan in mice. The extract shows potential in treating anxiety and other neurological disorders, possibly through the involvement of monoaminergic systems and GABA receptors.
JOURNAL OF ETHNOPHARMACOLOGY
(2023)
Article
Behavioral Sciences
Yixue Qin, Haoxuan Li, Yuqi Zhang, Jun-Li Cao, Wenxin Zhang, Hongxing Zhang
Summary: The addition of retigabine as an adjunctive treatment enhances the antidepressant effect of ketamine, allowing for a lower dose of ketamine to be effective in the forced swim test. Simultaneous administration of retigabine with ketamine significantly improves the duration and effectiveness of ketamine's antidepressant effect.
PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR
(2023)
Article
Neurosciences
Gonzalo Flores, Gabriel Daniel Flores-Gomez, Alfonso Diaz, Julio Cesar Penagos-Corzo, Tommaso Iannitti, Julio Cesar Morales-Medina
Summary: Aging is a complex process that can lead to neurodegenerative diseases and cognitive deficits. Understanding neural changes is critical for designing new therapies targeting aging and associated pathologies.
Article
Neurosciences
Julia Flores-Tochihuitl, Beatriz Marquez Villegas, Anahi Catalina Peral Lemus, Cristian Jesus Andraca Hernandez, Gonzalo Flores, Julio Cesar Morales-Medina
Summary: The study found that periodontitis affects neuroplasticity by decreasing total dendritic length in the NO of male rats, while diabetes increases spine number in both the NO and VPL and reduces TDL in the NO in both male and female rats. Periodontitis has a dimorphic effect in the NO, whereas diabetes induces a strong neuromorphological effect regardless of sex. Additionally, periodontitis has limited impact on neuronal morphology but significantly alters neural consequences in the VPL and NO when comorbid with diabetes.
Review
Environmental Sciences
Beniamino Palmieri, Veronica Corazzari, Maria Vadala, Annamaria Vallelunga, Julio Cesar Morales-Medina, Tommaso Iannitti
Summary: Multiple chemical sensitivity (MCS) is characterized by non-specific and recurring symptoms affecting multiple organs, with chemical intolerance being a key distinguishing feature. Current diagnosis relies on clinical symptoms as there are no specific diagnostic markers available, and more definite treatment strategies are required. Research on the pathophysiology of MCS, particularly focusing on brain networks, environmental pollution, and correlation with other pathologies, is ongoing to better understand and develop treatment strategies.
REVIEWS ON ENVIRONMENTAL HEALTH
(2021)
Article
Chemistry, Medicinal
Curt A. Dvorak, Dale A. Rudolph, Diane Nepomuceno, Lisa Dvorak, Brian Lord, Ian Fraser, Pascal Bonaventure, Timothy Lovenberg, Nicholas I. Carruthers
Summary: A novel dual 5-HT7/5-HT2 receptor antagonist, 3-(4-Fluorophenyl)-2-isopropyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene (4j), showed high affinity for both receptors with potential therapeutic efficacy in in vivo models for central 5-HT7 and 5-HT2A activity.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2021)
Article
Urology & Nephrology
Carlos E. Aguilar-Perez, Porfirio Gomora-Arrati, Barry R. Komisaruk, Maria Reyna Fuentes-Morales, Julio Cesar Morales-Medina, Oscar Gonzalez-Flores, Rosa Angelica Lucio
Summary: Copulation-induced analgesia is related to ejaculatory endophenotypes, with rapid and intermediate ejaculating rats exhibiting higher levels of analgesia during two consecutive ejaculatory series.
INTERNATIONAL JOURNAL OF IMPOTENCE RESEARCH
(2022)
Article
Neurosciences
Andrew H. Cooper, Naomi S. Hedden, Gregory Corder, Sydney R. Lamerand, Renee R. Donahue, Julio C. Morales-Medina, Lindsay Selan, Pranav Prasoon, Bradley K. Taylor
Summary: The experiment demonstrated that by intracerebroventricular injection of opioid receptor inhibitors, mechanical hypersensitivity can be reinstated, suggesting that MORs in the capsular subdivision of the right CeA prevent the transition from acute to chronic postoperative pain. Furthermore, it was found that systemic administration of naloxone and naltrexone in LS animals produced different effects compared to naive or sham controls.
JOURNAL OF NEUROSCIENCE RESEARCH
(2022)
Article
Behavioral Sciences
Julio Cesar Morales-Medina, Patricia Aguilar-Alonso, Alessandro Di Cerbo, Tommaso Iannitti, Gonzalo Flores
Summary: Schizophrenia is a complex disorder with unknown underlying mechanisms, where nitric oxide (NO) has emerged as a key signaling molecule. Various animal models of schizophrenia show alterations in NO levels, particularly in neurodevelopmental models, glutamatergic models with PCP administration, and genetic models with neuronal NOS knock-out mice. Treatment with NO donors or antipsychotics can reverse schizophrenia-related behavioral deficits, indicating potential therapeutic implications for targeting NO in schizophrenia.
BEHAVIOURAL BRAIN RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Aldo Efrain Gonzalez-Granillo, Dino Gnecco, Alfonso Diaz, Linda Garces-Ramirez, Fidel de la Cruz, Ismael Juarez, Julio Cesar Morales-Medina, Gonzalo Flores
Summary: The study shows that chronic curcumin treatment can improve learning and memory, increase synaptic density and dendritic branching, and reduce aging-related damages by regulating the expression of certain proteins.
JOURNAL OF CHEMICAL NEUROANATOMY
(2022)
Article
Pharmacology & Pharmacy
Anthony W. Harrington, Changlu Liu, Naomi Phillips, Diane Nepomuceno, Chester Kuei, Joseph Chang, Weixuan Chen, Steven W. Sutton, Daniel O'Malley, Ly Pham, Xiang Yao, Siquan Sun, Pascal Bonaventure
Summary: The study suggests that oxysterols, including 24S-HC, could be physiological activators for GPR17, regulating oligodendrocyte progenitor cell differentiation and myelination through receptor activation.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Julio Cesar Morales-Medina, Nicola Pugliese, Alessandro Di Cerbo, Claudia Zizzadoro, Tommaso Iannitti
Summary: Studies in mice have shown that constitutive activation of endogenous opioid signaling leads to both endogenous analgesia and opioid dependence. This study aimed to determine if a similar pattern exists in rats. Rats with chronic inflammatory pain were treated with different doses of the opioid receptor inverse agonist naltrexone (NTX) and monitored for withdrawal behaviors. The response to NTX in the rat model was different from the mouse model, suggesting species-related differences in pharmacological response and highlighting the importance of species selection in preclinical pain research.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Leonardo Aguilar-Hernandez, Ricardo Alejandre, Julio Cesar Morales-Medina, Tommaso Iannitti, Gonzalo Flores
Summary: Aging is a natural process characterized by the accumulation of cellular damage and debris. It is associated with oxidative stress, cellular senescence, sustained inflammation, and DNA damage, leading to morphological and functional decline. The atrophy is mainly observed in high metabolic tissues such as the brain, particularly in regions related to cognitive behavior. This article reviews the cellular processes triggering aging, distinguishes between normal and pathological aging, and discusses the use of supplements with antioxidant and anti-inflammatory properties in reducing cognitive decline.
JOURNAL OF CHEMICAL NEUROANATOMY
(2023)
Article
Neurosciences
Gonzalo Flores, Maria de Jesus Gomez-Villalobos, Tommaso Iannitti, Julio Cesar Morales-Medina
Summary: Olfaction is a complex physiological process that affects the central nervous system and is involved in emotional processes. The olfactory bulbs in rats are connected to various regions of the central nervous system, such as the nucleus accumbens and caudate-putamen, which receive important dopaminergic input. Dopamine has been found to be related to anxiety-related behaviors. This study investigated the effects of neonatal olfactory bulbectomy on anxiety-related behavior in rats using the elevated plus maze, as well as the expression of dopaminergic receptors in the nucleus accumbens and caudate-putamen. The results showed that neonatal olfactory bulbectomy increased open arm entries in the elevated plus maze in post-pubertal rats, indicating an anxiolytic effect. The expression of D2-like binding in the nucleus accumbens shell and D3 binding in the nucleus accumbens core increased in pre-pubertal rats after olfactory bulbectomy. However, D3 binding was reduced in the olfactory tubercle and islands of Calleja in olfactory bulbectomized rats at post-pubertal ages. These findings suggest that alterations in dopaminergic receptor expression may contribute to the observed behavioral changes in olfactory bulbectomized rats.
Meeting Abstract
Neurosciences
Benjamin Throesch, Michelle Wennerholm, Pascal Bonaventure, Grace Woodruff
NEUROPSYCHOPHARMACOLOGY
(2022)
Article
Engineering, Biomedical
Beniamino Palmieri, Maria Vadala, Simone Ugo Urso, Laura Ornella Baldini, Caterina Fanelli, Julio Cesar Morales-Medina, Tommaso Iannitti
Summary: This study evaluated the efficacy of sclerofoam-assisted laser treatment combined with nutraceutical administration for the treatment of chronic venous insufficiency. The results showed promising outcomes in improving symptoms and patient conditions.
LASERS IN MEDICAL SCIENCE
(2022)
Meeting Abstract
Neurosciences
Benjamin Throesch, Michelle Wennerholm, Pascal Bonaven-Ture, Grace Woodruff
NEUROPSYCHOPHARMACOLOGY
(2021)
Article
Endocrinology & Metabolism
Andreia Biolchi Mayer, Henrique de Oliveira Amaral, Danilo Gustavo R. de Oliveira, Gabriel Avohay Alves Campos, Priscilla Galante Ribeiro, Solange Cristina Rego Fernandes, Adolfo Carlos Barros de Souza, Raffael Hinio Araijo de Castro, Anamelia Lorenzetti Bocca, Marcia Renata Mortari
Summary: This study synthesized three bioinspired peptides based on fraternine and tested their effects in a Parkinson's disease model. The peptides fra-10 and fra-14 improved motor coordination, but most of the peptides were toxic at the applied doses. All three peptides reduced the intensity of lesion-induced rotations. The peptide fra-24 increased the number of TH+ neurons in the substantia nigra and reduced the concentration of the cytokine TNF-alpha, suggesting it has neuroprotective effects in Parkinson's disease.
