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Open AccessArticle

Early Blockade of CB1 Receptors Ameliorates Schizophrenia-like Alterations in the Neurodevelopmental MAM Model of Schizophrenia

by Tibor Stark, Fabio Arturo Iannotti, Serena Di Martino, Martina Di Bartolomeo, Jana Ruda-Kucerova, Fabiana Piscitelli, Carsten T. Wotjak, Claudio D’Addario, Filippo Drago, Vincenzo Di Marzo and Vincenzo Micale

Biomolecules 2022, 12(1), 108; https://0-doi-org.brum.beds.ac.uk/10.3390/biom12010108 - 10 Jan 2022

Cited by 9 | Viewed by 2877

Abstract

In agreement with the neurodevelopmental hypothesis of schizophrenia, prenatal exposure of Sprague-Dawley rats to the antimitotic agent methylazoxymethanol acetate (MAM) at gestational day 17 produces long-lasting behavioral alterations such as social withdrawal and cognitive impairment in adulthood, mimicking a schizophrenia-like phenotype. These abnormalities [...] Read more.

In agreement with the neurodevelopmental hypothesis of schizophrenia, prenatal exposure of Sprague-Dawley rats to the antimitotic agent methylazoxymethanol acetate (MAM) at gestational day 17 produces long-lasting behavioral alterations such as social withdrawal and cognitive impairment in adulthood, mimicking a schizophrenia-like phenotype. These abnormalities were preceded at neonatal age both by the delayed appearance of neonatal reflexes, an index of impaired brain maturation, and by higher 2-arachidonoylglycerol (2-AG) brain levels. Schizophrenia-like deficits were reversed by early treatment [from postnatal day (PND) 2 to PND 8] with the CB1 antagonist/inverse agonist AM251 (0.5 mg/kg/day). By contrast, early CB1 blockade affected the behavioral performance of control rats which was paralleled by enhanced 2-AG content in the prefrontal cortex (PFC). These results suggest that prenatal MAM insult leads to premorbid anomalies at neonatal age via altered tone of the endocannabinoid system, which may be considered as an early marker preceding the development of schizophrenia-like alterations in adulthood. Full article

(This article belongs to the Special Issue State-of-the-Art of the New Pharmacological Targets for Treating Chronic Neuropsychiatric Disorders in Italy)

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12 pages, 275 KiB

Open AccessCommunication

Chronic Pain in the Elderly: Mechanisms and Distinctive Features

by Andrea Tinnirello, Silvia Mazzoleni and Carola Santi

Biomolecules 2021, 11(8), 1256; https://0-doi-org.brum.beds.ac.uk/10.3390/biom11081256 - 23 Aug 2021

Cited by 37 | Viewed by 8370

Abstract

Background: Chronic pain is a major issue affecting more than 50% of the older population and up to 80% of nursing homes residents. Research on pain in the elderly focuses mainly on the development of clinical tools to assess pain in patients with [...] Read more.

Background: Chronic pain is a major issue affecting more than 50% of the older population and up to 80% of nursing homes residents. Research on pain in the elderly focuses mainly on the development of clinical tools to assess pain in patients with dementia and cognitive impairment or on the efficacy and tolerability of medications. In this review, we searched for evidence of specific pain mechanisms or modifications in pain signals processing either at the cellular level or in the central nervous system. Methods: Narrative review. Results: Investigation on pain sensitivity led to conflicting results, with some studies indicating a modest decrease in age-related pain sensitivity, while other researchers found a reduced pain threshold for pressure stimuli. Areas of the brain involved in pain perception and analgesia are susceptible to pathological changes such as gliosis and neuronal death and the effectiveness of descending pain inhibitory mechanisms, particularly their endogenous opioid component, also appears to deteriorate with advancing age. Hyperalgesia is more common at older age and recovery from peripheral nerve injury appears to be delayed. In addition, peripheral nociceptors may contribute minimally to pain sensation at either acute or chronic time points in aged populations. Conclusions: Elderly subjects appear to be more susceptible to prolonged pain development, and medications acting on peripheral sensitization are less efficient. Pathologic changes in the central nervous system are responsible for different pain processing and response to treatment. Specific guidelines focusing on specific pathophysiological changes in the elderly are needed to ensure adequate treatment of chronic pain conditions. Full article

(This article belongs to the Special Issue State-of-the-Art of the New Pharmacological Targets for Treating Chronic Neuropsychiatric Disorders in Italy)

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8 pages, 219 KiB

Open AccessOpinion

Buprenorphine: Far Beyond the “Ceiling”

by Rosmara Infantino, Consalvo Mattia, Pamela Locarini, Antonio Luigi Pastore, Sabatino Maione and Livio Luongo

Biomolecules 2021, 11(6), 816; https://0-doi-org.brum.beds.ac.uk/10.3390/biom11060816 - 31 May 2021

Cited by 10 | Viewed by 11375

Abstract

Chronic pain, including neuropathic pain, represents an untreated disease with important repercussions on the quality of life and huge costs on the national health system. It is well known that opioids are the most powerful analgesic drugs, but they represent the second or [...] Read more.

Chronic pain, including neuropathic pain, represents an untreated disease with important repercussions on the quality of life and huge costs on the national health system. It is well known that opioids are the most powerful analgesic drugs, but they represent the second or third line in neuropathic pain, that remain difficult to manage. Moreover, these drugs show several side effects that limit their use. In addition, opioids possess addictive properties that are associated with misuse and drug abuse. Among available opioids compounds, buprenorphine has been suggested advantageous for a series of clinical reasons, including the effectiveness in neuropathic pain. Some properties are partly explained by its unique pharmacological characteristics. However, questions on the dynamic profile remain to be answered. Pharmacokinetics optimization strategies, and additional potentialities, are still to be explored. In this paper, we attempt to conceptualize the potential undiscovered dynamic profile of buprenorphine. Full article

(This article belongs to the Special Issue State-of-the-Art of the New Pharmacological Targets for Treating Chronic Neuropsychiatric Disorders in Italy)

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