Chronic lorcaserin treatment reverses the nicotine withdrawal-induced disruptions to behavior and maturation in developing neurons in the hippocampus of rats

Preclinical data have shown that treatment with serotonin (5-HT)2C receptor agonists inhibits the behavioral effects of nicotine, including self-administration, reinstatement, and locomotor responses to nicotine. Since the data on the effects of 5-HT2C receptor agonism on nicotine withdrawal signs are limited, we aimed to investigate whether 5-HT2C receptor agonism alleviated the behavioral and neurobiochemical (hippocampal neurogenesis) consequences of nicotine withdrawal in Sprague-Dawley rats. Our data indicate that withdrawal from nicotine self-administration induced locomotor hyperactivity, lengthened immobility time (the forced swim test), induced ‘drug-seeking’ behavior and deficits in cognition-like behavior (the novel object recognition task). A two-week exposure to the 5-HT2C receptor agonist lorcaserin attenuated locomotor hyperactivity and induced recovery from depression-like behavior. Analyses of brain slices from nicotine-withdrawn animals revealed that lorcaserin treatment recovered the reduced number of doublecortin (DCX)-positive cells, but it did not affect the number of Ki-67- or 5-bromo-2’-deoxyuridine (BrdU)-positive cells or the maturation of proliferating neurons in drug-weaned rats. To summarize, we show that lorcaserin alleviated locomotor responses and depression-like state during nicotine withdrawal. We propose that the modulatory effect of lorcaserin on the ‘affective’ aspects of nicotine cessation may be linked to the positive changes caused by the compound in hippocampal neurogenesis during nicotine withdrawal

Evidence for cytoprotective effect of carbon monoxide donor in the development of acute esophagitis leading to acute esophageal epithelium lesions

Exposure to acidic gastric content due to malfunction of lower esophageal sphincter leads to acute reflux esophagitis (RE) leading to disruption of esophageal epithelial cells. Carbon monoxide (CO) produced by heme oxygenase (HMOX) activity or released from its donor, tricarbonyldichlororuthenium (II) dimer (CORM-2) was reported to protect gastric mucosa against acid-dependent non-steroidal anti-inflammatory drug-induced damage. Thus, we aimed to investigate if CO affects RE-induced esophageal epithelium lesions development. RE induced in Wistar rats by the ligation of a junction between pylorus and forestomach were pretreated i.g. with vehicle CORM-2; RuCl3; zinc protoporphyrin IX, or hemin. CORM-2 was combined with NG-nitro-L-arginine (L-NNA), indomethacin, capsazepine, or capsaicin-induced sensory nerve ablation. Esophageal lesion score (ELS), esophageal blood flow (EBF), and mucus production were determined by planimetry, laser flowmetry, histology. Esophageal Nrf-2, HMOXs, COXs, NOSs, TNF-α and its receptor, IL-1 family and IL-1 receptor antagonist (RA), NF-κB, HIF-1α, annexin-A1, suppressor of cytokine signaling (SOCS3), TRPV1, c-Jun, c-Fos mRNA/protein expressions, PGE2, 8-hydroxy-deoxyguanozine (8-OHdG) and serum COHb, TGF-β1, TGF-β2, IL-1β, and IL-6 content were assessed by PCR, immunoblotting, immunohistochemistry, gas chromatography, ELISA or Luminex platform. Hemin or CORM-2 alone or combined with L-NNA or indomethacin decreased ELS. Capsazepine or capsaicin-induced denervation reversed CORM-2 effects. COHb blood content, esophageal HMOX-1, Nrf-2, TRPV1 protein, annexin-A1, HIF-1α, IL-1 family, NF-κB, c-Jun, c-Fos, SOCS3 mRNA expressions, and 8-OHdG levels were elevated while PGE2 concentration was decreased after RE. CO donor-maintained elevated mucosal TRPV1 protein, HIF-1 α, annexin-A1, IL-1RA, SOCS3 mRNA expression, or TGF-β serum content, decreasing 8-OHdG level, and particular inflammatory markers expression/concentration. CORM-2 and Nrf-2/HMOX-1/CO pathway prevent esophageal mucosa against RE-induced lesions, DNA oxidation, and inflammatory response involving HIF-1α, annexin-A1, SOCS3, IL-1RA, TGF-β-modulated pathways. Esophagoprotective and hyperemic CO effects are in part mediated by afferent sensory neurons and TRPV1 receptors activity with questionable COX/PGE2 or NO/NOS systems involvement

Wymiary przestrzeni życiowej współczesnej rodziny

Praca recenzowana / peer-reviewed pape

Activity antiarrthmic and hipotensive of 2-aminopropanol

The thesis was discussed sympathetic nervous system impact on the cardiovascular system and the pathogenesis of cardiovascular diseases, with particular emphasis on conditions such as hypertension and arrhythmia. These were β-blockers, medicines used in hypertensive disease: characterization of their mechanism of action, chemical structure, steroizmoerii incidence and its impact on pharmacological activity, indicating the greatest role of the new β-blockers, carvedilol, ie third generation. Tests were performed on rats to investigate the hypotensive and antiarrhythmic activity of a new derivative 2-aminopropanolu 2,3-DMIND tj. :1-(1-H-indol-4-iloksy)-3-[[2-(2,3-dimetoksyfenoksy)etylo]amino]propan-2-ol, a compound of similar structure to carvedilolW pracy został omówiony wpływ układu wspłczólnego na układ krążenia i patogenezę chorób sercowo-naczyniowych, ze szczególnym uwzględniem takich schorzeń jak nadciśnienie oraz arytmia. Opisane zostały β-adrenolityki -leki stosowane w chorobie nadciśnieniowej:ich charakterystykę mechanizm działania,budowę chemiczną, wystepowanie steroizmoerii i jej wpływ na aktywność framkologiczną, z zaznaczeniem największej roli nowych β-blokerów, III generacji tj. karwedilol. Wykonane zostały badania na szczurach , mające na celu zbadanie aktywności hipotensyjnej i przeciwarytmicznej nowej pochodnej 2-aminopropanolu 2,3-DMIND tj. :1-(1-H-indol-4-iloksy)-3-[[2-(2,3-dimetoksyfenoksy)etylo]amino]propan-2-olu-związku o zbliżonej strukturze do karwedilol