RESUMO
Linagliptin is a selective dipeptidyl peptidase-4 (DPP-4) inhibitor that indirectly elevates the glucagon-like peptide-1 (GLP-1) level. The aim of the present study was to check whether linagliptin has an influence on neurotransmission in rat brain. Rats were acutely and chronically exposed to linagliptin (10 and 20 mg/kg, intraperitoneally (i.p.)). Twenty-four hours later, the striatum and hippocampus were selected for further studies. In neurochemical experiments, using high-performance liquid chromatography with electrochemical detection (HPLC-ED), the concentrations of three major neurotransmitters-dopamine, serotonin and noradrenaline-and their metabolites were measured. The analysis of mRNA expression of dopamine (D1 and D2), serotonin (5-HT-1 and 5-HT-2) and noradrenaline (α1 and α2a) receptors was also investigated using real-time quantitative reverse transcription polymerase chain reaction (RQ-PCR) in the same brain areas. Linagliptin has the ability to influence the dopaminergic system. In the striatum, the elevation of dopamine and its metabolites was observed after repeated administration of that linagliptin, and in the hippocampus, a reduction in dopamine metabolism was demonstrated. Acute linagliptin exposure increases the serotonin level in both areas, while after chronic linagliptin administration a tendency for the mRNA expression of serotoninergic receptors (5-HT1A and 5-HT2A) to increase was observed. A single instance of exposure to linagliptin significantly modified the noradrenaline level in the striatum and intensified noradrenaline turnover in the hippocampus. The recognition of the interactions in the brain between DPP-4 inhibitors and neurotransmitters and/or receptors is a crucial step for finding novel discoveries in the pharmacology of DPP-4 inhibitors and raises hope for further applications of DPP-4 inhibitors in clinical practices.
Assuntos
Inibidores da Dipeptidil Peptidase IV , Linagliptina , Ratos , Animais , Linagliptina/farmacologia , Inibidores da Dipeptidil Peptidase IV/farmacologia , Serotonina , Dopamina , Norepinefrina , Dipeptidil Peptidase 4/metabolismo , Hipocampo/metabolismo , Neurotransmissores , RNA MensageiroRESUMO
Cannabidiol (CBD), a phytocannabinoid, appeared to satisfy several criteria for a safe approach to preventing drug-taking behavior, including opioids. However, most successful preclinical and clinical results come from studies in adult males. We examined whether systemic injections of CBD (10 mg/kg, i.p.) during extinction of oxycodone (OXY, 3 mg/kg, i.p.) induced conditioned place preference (CPP) could attenuate the reinstatement of CPP brought about by OXY (1.5 mg/kg, i.p.) priming in adolescent rats of both sexes, and whether this effect is sex dependent. Accordingly, a priming dose of OXY produced reinstatement of the previously extinguished CPP in males and females. In both sexes, this effect was linked to locomotor sensitization that was blunted by CBD pretreatments. However, CBD was able to prevent the reinstatement of OXY-induced CPP only in adolescent males and this outcome was associated with an increased cannabinoid 1 receptor (CB1R) and a decreased mu opioid receptor (MOR) expression in the prefrontal cortex (PFC). The reinstatement of CCP in females was associated with a decreased MOR expression, but no changes were detected in CB1R in the hippocampus (HIP). Moreover, CBD administration during extinction significantly potentialized the reduced MOR expression in the PFC of males and showed a tendency to potentiate the reduced MOR in the HIP of females. Additionally, CBD reversed OXY-induced deficits of recognition memory only in males. These results suggest that CBD could reduce reinstatement to OXY seeking after a period of abstinence in adolescent male but not female rats. However, more investigation is required.
Assuntos
Canabidiol , Oxicodona , Receptor CB1 de Canabinoide , Receptores Opioides mu , Animais , Canabidiol/farmacologia , Masculino , Feminino , Oxicodona/farmacologia , Ratos , Receptor CB1 de Canabinoide/metabolismo , Receptores Opioides mu/metabolismo , Córtex Pré-Frontal/efeitos dos fármacos , Córtex Pré-Frontal/metabolismo , Analgésicos Opioides/farmacologia , Condicionamento Psicológico/efeitos dos fármacosRESUMO
Children with fetal alcohol spectrum disorders (FASDs) demonstrate deficits in social functioning that contribute to early withdrawal from school and delinquency, as well as the development of anxiety and depression. Dopamine is involved in reward, motivation, and social behavior. Thus, we evaluated whether neonatal ethanol exposure (in an animal model of FASDs) has an impact on social recognition memory using the three-chamber social novelty discrimination test during early and middle adolescence in male and female rats, and whether the modafinil analog, the novel atypical dopamine reuptake inhibitor CE-123, can modify this effect. Our study shows that male and female rats neonatally exposed to ethanol exhibited sex- and age-dependent deficits in social novelty discrimination in early (male) and middle (female) adolescence. These deficits were specific to the social domain and not simply due to more general deficits in learning and memory because these animals did not exhibit changes in short-term recognition memory in the novel object recognition task. Furthermore, early-adolescent male rats that were neonatally exposed to ethanol did not show changes in the anxiety index but demonstrated an increase in locomotor activity. Chronic treatment with CE-123, however, prevented the appearance of these social deficits. In the hippocampus of adolescent rats, CE-123 increased BDNF and decreased its signal transduction TrkB receptor expression level in ethanol-exposed animals during development, suggesting an increase in neuroplasticity. Thus, selective dopamine reuptake inhibitors, such as CE-123, represent interesting drug candidates for the treatment of deficits in social behavior in adolescent individuals with FASDs.
Assuntos
Compostos Benzidrílicos , Transtornos do Espectro Alcoólico Fetal , Interação Social , Humanos , Adolescente , Criança , Gravidez , Feminino , Masculino , Animais , Ratos , Etanol/efeitos adversos , Inibidores da Captação de Dopamina , DopaminaRESUMO
Postnatal depression is a common and severe complication of childbirth. It is an important public health problem with significant implications for both mothers and children. The exact mechanisms underlying and the factors influencing the occurrence of postnatal depression remain unclear. The literature suggests that certain dietary deficiencies during pregnancy and the postnatal period may contribute to a greater risk of maternal depression. This review focuses on the role of selenium in postnatal depression. It collects evidence from published interventional and observational studies investigating the relationship between selenium intake during the antenatal and postnatal periods and the mental status of postpartum women and summarises information about biological mechanisms that may underlie the association between selenium status and postnatal depression. The review includes studies identified through electronic searches of Medline (via PubMed) and Google Scholar databases until December 2023. Despite the small number of relevant studies and their potential methodological limitations, the findings suggest that optimizing selenium status may support the prevention and treatment of postnatal depression. Further longitudinal and interventional studies are necessary to confirm the clinical significance of these effects.