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Special Issue "Advances in Behavioral Psychopharmacology"

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A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Pharmacology".

Deadline for manuscript submissions: 31 October 2023 | Viewed by 4446

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Special Issue Editor

Dr. Agnieszka Pałucha-Poniewiera

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Guest Editor

Institute of Pharmacology, the Polish Academy of Sciences, Krakow, Poland
Interests: antidepressants; behavioral psychopharmacology; chronic stress; depression; ketamine; mGlu receptors

Special Issue Information

Dear Colleagues,

According to WHO the global burden of mental disorders continues to grow, despite decades of detailed research in the field of neuroscience, using modern methods, including brain imaging techniques. Depression, bipolar disorder, schizophrenia, and other psychoses, dementia, developmental disorders, including autism, and other disorders related to abnormal emotions, thoughts, perceptions, and behavior still pose a huge global medical, social, and economic problem. Behavioral research using animal models of mental illnesses or screening tests used for finding potential drugs, help in the search for new forms of therapy. Animal models of mental disorders or at least some disease symptoms, although imperfect, also help to determine the pathomechanism of mental illnesses, the study of which is very difficult in patients. Substance use disorders including drugs addiction, related to the compulsive search and intake of addictive substances as a result of loss of control over the behavior are also a serious problem to public health. Here, research in the field of behavioral psychopharmacology also offers huge opportunities in the study of the mechanisms of these pathological states, as well as new therapeutic strategies. Despite great achievements in behavioral psychopharmacology, new efforts are still needed to cope with the growing problem of the spread of mental illness and modern techniques appear to be essential in dealing with these challenges.

In this Special Issue, we would like to gather experts in the field of behavioral psychopharmacology that focus on the discovery of new therapeutic agents and strategies and on the studies of the mechanisms of changes in animal behavior in response to environmental fluctuations and pharmacological interventions. Original research articles, as well as stimulating reviews that provide new interpretations of the up-to-date results and extant literature are highly welcome.

Dr. Agnieszka Pałucha-Poniewiera
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceuticals is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2200 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

addiction
behavioral models
behavioral pharmacology
cognition
depression
drug abuse
memory
psychoactive drugs

Published Papers (4 papers)

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Research

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Open AccessArticle

Targeting the Endoplasmic Reticulum Stress-Linked PERK/GRP78/CHOP Pathway with Magnesium Sulfate Attenuates Chronic-Restraint-Stress-Induced Depression-like Neuropathology in Rats

and

Pharmaceuticals 2023, 16(2), 300; https://doi.org/10.3390/ph16020300 - 15 Feb 2023

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Abstract

Magnesium sulfate has demonstrated marked neuroprotection in eclampsia, hypoxia, stroke, and post-traumatic brain injury rodent models. However, its potential impact against chronic-restraint-stress (CRS)-induced depression-like neuropathology and associated alterations in endoplasmic reticulum (ER) stress have not been adequately examined. The present study aimed to investigate the neuroprotective potential of magnesium sulfate in a rat model of CRS-triggered depression-like behavioral disturbance and the underlying molecular mechanisms. Herein, CRS was induced by placing rats into restraining tubes for 6 h/day for 21 days and the animals were intraperitoneally injected with magnesium sulfate (100 mg/kg/day) during the study period. After stress cessation, the depression-like behavior was examined by the open-field test, sucrose preference test, and forced swimming test. The present data demonstrated that CRS triggered typical depression-like behavioral changes which were confirmed by the Z-normalization scores. Mechanistically, serum circulating corticosterone levels spiked, and the hippocampi of CRS-exposed animals demonstrated a significant decline in serotonin, norepinephrine, and dopamine neurotransmitters. At the molecular level, the hippocampal pro-inflammatory TNF-alpha and IL-1β cytokines and the oxidative stress marker 8-hydroxy-2′-deoxyguanosine (8-HG) increased in stressed animals. In tandem, enhancement of hippocampal ER stress was evidenced by the activation of iNOS/PERK/GRP78/CHOP axis seen by increased protein expression of iNOS, PERK, GRP78, and CHOP signal proteins in the hippocampi of stressed rats. Interestingly, magnesium sulfate administration attenuated the depression-like behavioral outcomes and the histopathological changes in the brain hippocampi. These favorable actions were driven by magnesium sulfate’s counteraction of corticosterone spike, and hippocampal neurotransmitter decline, alongside the attenuation of neuroinflammation, pro-oxidation, and ER stress. In conclusion, the current results suggest the promising neuroprotective/antidepressant actions of magnesium sulfate in CRS by dampening inflammation, ER stress, and the associated PERK/GRP78/CHOP pathway. Full article

(This article belongs to the Special Issue Advances in Behavioral Psychopharmacology)

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Open AccessArticle

The Antidepressant-like Activity and Cognitive Enhancing Effects of the Combined Administration of (R)-Ketamine and LY341495 in the CUMS Model of Depression in Mice Are Related to the Modulation of Excitatory Synaptic Transmission and LTP in the PFC

Agnieszka Pałucha-Poniewiera

Bartosz Bobula

and

Anna Rafało-Ulińska

Pharmaceuticals 2023, 16(2), 288; https://doi.org/10.3390/ph16020288 - 14 Feb 2023

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Abstract

(S)-Ketamine is the first rapid-acting antidepressant drug (RAAD) introduced for the treatment of depression. However, research is still being carried out on the search for further RAADs that will be not only effective but also safe to use. Recent data have indicated that the combined administration of (R)-ketamine and the mGlu_2/3 receptor antagonist LY341495 (mixRL) induces rapid and sustained effects in the chronic unpredictable mild stress (CUMS) model of depression in mice, and the use of this drug combination is associated with a low risk of undesirable effects. Considering the possible influence of stress on cortical plasticity and, on the other hand, the role of this plasticity in the mechanism of action of ketamine, we decided to investigate whether mixed RL affects synaptic plasticity in the prefrontal cortex (PFC) in the CUMS model of depression using electrophysiological techniques and explore whether these effects are related to memory impairments. Using behavioral methods, we found that a single administration of mixRL reversed CUMS-induced PFC-dependent memory deficits and alleviated depression-like effects induced by CUMS. In turn, electrophysiological experiments indicated that the amplitude of field potentials as well as paired-pulse responses in CUMS mice were increased, and mixRL was found to reverse these effects. Additionally, the magnitude of long-term potentiation (LTP) was reduced in CUMS mice, and mixRL was shown to restore this parameter. In summary, mixRL appeared to exert its antidepressant effects and cognitive enhancing effects in a mouse model of depression, at least in part, by mechanisms involving modulation of glutamatergic transmission and LTP in the PFC. Full article

(This article belongs to the Special Issue Advances in Behavioral Psychopharmacology)

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Open AccessCommunication

The Effects of Positive Allosteric Modulators of α7–nAChR on Social Play Behavior in Adolescent Rats Prenatally Exposed to Valproic Acid

Kinga Gzielo

and

Agnieszka Nikiforuk

Pharmaceuticals 2022, 15(11), 1417; https://doi.org/10.3390/ph15111417 - 16 Nov 2022

Viewed by 1105

Abstract

There is still no effective treatment that addresses the core symptoms of autism spectrum disorders (ASD), including social and communication deficits. A comprehensive body of evidence points to the cholinergic system, including alpha7–nicotinic acetylcholine receptors (α7–nAChRs), as a potential target of pharmacotherapy. A promising approach is based on positive allosteric modulators (PAMs) of these receptors due to their advantages over direct agonists. Nevertheless, α7 n–AChR ligands have not been widely studied in the context of autism. Therefore, using one of the most widely used rodent models of ASD, that is, prenatal exposure to valproic acid (VPA), we examined the impact of α7–nAChR PAMs (PNU–120596 and CCMI) on socio-communicative behavior during social play in adolescent male and female rats. The current study demonstrated that PAM treatment affected certain aspects of socio-communicative behavior in adolescent rats. Accordingly, PNU–120596 ameliorated deficient play abilities in VPA-exposed males, as revealed by increased play time during a social encounter. In addition, this compound enhanced the emission of ultrasonic vocalizations that accompanied playful interactions. Moreover, we observed the overall effect of PNU–120596 on non-playful forms of social behavior (i.e., social exploration) and acoustic parameters (i.e., the duration) of emitted calls. The present results suggest the ability of α7–nAChR PAMs to facilitate socio-communicative behavior in adolescent rats. Full article

(This article belongs to the Special Issue Advances in Behavioral Psychopharmacology)

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Review

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Open AccessReview

Progesterone and Its Metabolites Play a Beneficial Role in Affect Regulation in the Female Brain

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Pharmaceuticals 2023, 16(4), 520; https://doi.org/10.3390/ph16040520 - 31 Mar 2023

Viewed by 1088

Abstract

Premenstrual dysphoric disorder is a female affective disorder that is defined by mood symptoms. The condition is linked to unstable progesterone concentrations. Progestin supplementation is given in cases of threatened or recurrent miscarriage and for luteal phase support. Progesterone is essential for implantation, immune tolerance, and modulation of uterine contractility. For a long time, the administration of progestins was associated with an unfavorable impact on mood, leading to negative affect, and, therefore, was contraindicated in existing mood disorders. Establishing the role of the natural progesterone derivative allopregnanolone in advances in the treatment of postpartum depression has shed new light on the general pathophysiology of mood disorders. Allopregnanolone directly interacts with gamma-aminobutyric acid type A (GABA-A) receptors even at nanomolar concentrations and induces significant anti-depressant, anti-stress, sedative, and anxiolytic effects. Postpartum depression is caused by a rapid drop in hormones and can be instantly reversed by the administration of allopregnanolone. Premenstrual dysphoric disorder can also be considered to result from insufficient neuroactive steroid action due to low progesterone derivative concentration, unstable hormone levels, or decreased receptor sensitivity. The decrease in progesterone levels in perimenopause is also associated with affective symptoms and an exacerbation of some psychosomatic syndromes. Bioidentical progesterone supplementation encounters several obstacles, including limited absorption, first-pass effect, and rapid metabolism. Hence, non-bioidentical progestins with better bioavailability were widely applied. The paradoxical, unfavorable effect of progestins on mood can be explained by the fact that progestins suppress ovulation and disturb the endocrine function of the ovary in the luteal phase. Moreover, their distinct chemical structure prevents their metabolism to neuroactive, mood-improving derivatives. A new understanding of progesterone-related mood disorders can translate the study results from case series and observational studies to cohort studies, clinical trials, and novel, effective treatment protocols being developed. Full article

(This article belongs to the Special Issue Advances in Behavioral Psychopharmacology)

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