Donor Pre-treatment With IL-1 Receptor Antagonist As A Strategy To Attenuate Inflammation In The Pancreas And Islets Of Brain Dead Non-Human Primates

Background: Central nervous system disorders such as anxiety, depression and epilepsy are characterized by sharing several molecular mechanisms in common and the involvement of the L-arginine/NO pathway in neurobehavioral studies with β-caryophyllene is still little discussed. Objectives: One of the objectives of the present study was to demonstrate the anxiolytic behavioral effect of β-caryophyllene (β-CBP) in female Swiss mice, as well as to investigate the molecular mechanisms underlying the results obtained. Methods: This study evaluated the neurobehavioral effects of β-CBP using the open field test, rota-rod test, elevated plus maze test, novelty suppressed feeding test, tail suspension test and forced swim test, as well as pilocarpine, pentylenetetrazole and isoniazid-induced epileptic seizure models. Results:: The results demonstrated that the neuropharmacological activities of β-CBP may involve benzodiazepine/GABAergic receptors, since the pre-treatment of β-CBP (200 mg/kg) associated with flumazenil (5 mg/kg, benzodiazepine receptor antagonist) and bicuculline (1 mg/kg, selective GABAA receptor antagonist) reestablished the anxiety parameters in the elevated plus-maze test, as well as the results of reduced latency to consume food in the novelty suppressed feeding test. In addition to benzodiazepine/GABAergic receptors, the neuropharmacological properties of β-CBP may be related to inhibition of nitric oxide synthesis, since pre-treatment with L-arginine (500- 750 mg/kg) reversed significantly the anxiolytic, antidepressant and anticonvulsant activities of β-CBP. Conclusion: The results obtained provide additional support in understanding the neuromolecular mechanisms underlying the anxiolytic, antidepressant and anticonvulsive properties of β-CBP in female Swiss mice.

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Mineralocorticoid receptor antagonist pre-treatment and early post-treatment to minimize reperfusion injury after ST-elevation myocardial infarction: The MINIMIZE STEMI trial

American Heart Journal ◽

10.1016/j.ahj.2019.02.005 ◽

2019 ◽

Vol 211 ◽

pp. 60-67 ◽

Cited By ~ 5

Author(s):

Heerajnarain Bulluck ◽

Georg M Fröhlich ◽

Jennifer M Nicholas ◽

Shah Mohdnazri ◽

Reto Gamma ◽

...

Keyword(s):

Myocardial Infarction ◽

Receptor Antagonist ◽

Reperfusion Injury ◽

Mineralocorticoid Receptor ◽

Post Treatment ◽

St Elevation Myocardial Infarction ◽

Mineralocorticoid Receptor Antagonist ◽

St Elevation ◽

Pre Treatment

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Stress hormones promote DNA damage in human oral keratinocytes

Scientific Reports ◽

10.1038/s41598-021-99224-w ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Vitor Bonetti Valente ◽

Diovana de Melo Cardoso ◽

Giseli Mitsuy Kayahara ◽

Giovana Barros Nunes ◽

Kellen Cristine Tjioe ◽

...

Keyword(s):

Dna Damage ◽

Glucocorticoid Receptor ◽

Receptor Antagonist ◽

Stress Hormones ◽

Oral Keratinocytes ◽

Dna Breaks ◽

Genotoxic Effects ◽

Beta Adrenergic ◽

Pre Treatment ◽

Antagonist Ru486

AbstractChronic stress increases the systemic levels of stress hormones norepinephrine and cortisol. As well as tobacco-specific carcinogen NNK (4-(methylnitrosamine)-1-(3-pyridyl)-1-butanone), they can induce expressive DNA damage contributing to the cancer development. However, it is unknown whether stress hormones have genotoxic effects in oral keratinocytes. This study investigated the effects of stress hormones on DNA damage in a human oral keratinocyte cell line (NOK-SI). NOK-SI cells stimulated with norepinephrine or cortisol showed higher DNA damage compared to untreated cells. Norepinephrine-induced DNA damage was reversed by pre-treatment with beta-adrenergic blocker propranolol. Cells treated with NNK combined to norepinephrine displayed reduced levels of caspases 3 and 7. Cortisol also reduced the activity of pro-apoptotic enzymes. NNK or norepinephrine promoted single-strand breaks and alkali-label side breaks in the DNA of NOK-SI cells. Pre-treatment of cells with propranolol abolished these effects. Carcinogen NNK in the presence or absence of cortisol also induced DNA damage of these cells. The genotoxic effects of cortisol alone and hormone combined with NNK were blocked partially and totally, respectively, by the glucocorticoid receptor antagonist RU486. DNA damage promoted by NNK or cortisol and carcinogen combined to the hormone led to intracellular γH2AX accumulation. The effects caused by NNK and cortisol were reversed by propranolol and glucocorticoid receptor antagonist RU486, respectively. Propranolol inhibited the oxidation of basis induced by NNK in the presence of DNA-formamidopyrimidine glycosylase. DNA breaks induced by norepinephrine in the presence or absence of NNK resulted in higher 8OHdG cellular levels. This effect was also induced through beta-adrenergic receptors. Together, these findings indicate that stress hormones induce DNA damage of oral keratinocytes and could contribute to oral carcinogenesis.

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Potential Mechanisms Involved in the Anticonvulsant Effect of Methanol Extract of Pyrenancantha staudtii in Mice

Central Nervous System Agents in Medicinal Chemistry ◽

10.2174/1871524920666200211113633 ◽

2020 ◽

Vol 20 (2) ◽

pp. 144-154

Author(s):

Olayemi K. Wakeel ◽

Oluropo B. Awosan ◽

Oyetunji T. Kolawole ◽

Akeem A. Ayankunle ◽

Olukunle J. Onaolapo ◽

...

Keyword(s):

Receptor Antagonist ◽

Anticonvulsant Activity ◽

Methanol Extract ◽

Stem Bark ◽

Potential Effect ◽

Bark Extract ◽

Anticonvulsant Effect ◽

Dependent Manner ◽

Onset Of Action ◽

Pre Treatment

Objective: To determine the potential effect of Pyrenancantha staudtii extract on experimentally induced seizures in mice and to evaluate the role of benzodiazepines, naloxone, and serotonin within these pathways. Methods: Animal behaviours were evaluated using open field, hexobarbitone-induced sleep model, and anticonvulsant activity using picrotoxin-, or strychnine-, or isoniazid-induced convulsions. Attempt to understand the mode of action of the anticonvulsant activity of the plant, three notable antagonists (flumazenil, 3 mg/kg; naloxone 5 mg/kg, i.p., and cyproheptadine, 4 mg/kg, i.p) were used. Results: The results revealed a significant (p < 0.05) reduction in the frequency of rearing and grooming episodes compared with the control. The extract of P. staudtii potentiates the sleeping time of hexobarbitone-induced hypnosis in a dose-related manner. P. staudtii stem bark extracts significantly (p<0.05) prolonged the onset of a seizure and attenuated the duration of seizure in a dose-dependent manner in picrotoxin- and or isoniazid-induced seizures. While, P. staudtii stem bark extract at all doses (100, 200, and 400 mg kg-1) though significantly prolonged the onset of action, but did not confer any significant changes on the duration, as well as mortality in this strychnine-induced seizure model. However, the anticonvulsant activity of the methanolic extract of P. staudtii was significantly reversed following intraperitoneal pre-treatment with flumazenil (GABA receptor antagonist) and naloxone (opioid receptor antagonist) but not cyproheptadine (5-HT2 receptor antagonist) in picrotoxin-induced convulsion. Conclusion: The data obtained suggest that methanol extract of P. staudtii possessed significant anticonvulsant effect, thereby confirming the traditional uses of P. staudtii in the treatment of epilepsy; mechanisms of which could involve the interaction with GABAergic and or opioidergic system.

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Investigation of Antidepressant, Anxiolytic and Sedative Activities of the Aqueous Leaf Extract of Musa sapientum Linn. (Banana; Musaceae)

Drug Research ◽

10.1055/a-0651-7978 ◽

2018 ◽

Vol 69 (03) ◽

pp. 136-143 ◽

Cited By ~ 1

Author(s):

Olanrewaju Salako ◽

Abidemi Akindele ◽

Aishat Balogun ◽

Olufunmilayo Adeyemi

Keyword(s):

Receptor Antagonist ◽

Leaf Extract ◽

Dopamine D2 Receptor ◽

Anxiolytic Effect ◽

Antidepressant Effect ◽

Adrenoceptor Antagonist ◽

Musa Sapientum ◽

Aqueous Leaf Extract ◽

Hole Board ◽

Pre Treatment

Abstract Background Musa sapientum Linn. (Musaceae) is used in traditional African medicine in the management of mental disorders. This study was conducted to evaluate the central nervous system activities of the aqueous leaf extract of M. sapientum (MS). Materials and methods MS (50, 100 and 200 mg/kg, p.o.) was administered to separate groups of mice 1 h before behavioural studies. The antidepressant effect was studied using the forced swimming test (FST) and tail suspension test (TST) while the elevated plus maze (EPM) and the hole-board tests were used to evaluate the anxiolytic effect. The probable mechanism of antidepressant-like effect was also investigated. Results MS (50, 100 and 200 mg/kg) produced significant (P<0.0001) reduction in the duration of immobility with peak effect at 200 mg/kg (79.6%) in FST and 66.9 % in TST respectively when compared with control. The pre-treatment of mice with prazosin (α1-adrenoceptor antagonist, 62.5 µg/kg, i.p.) and sulpiride (dopamine D2 receptor antagonist, 50 mg/kg, i.p.) significantly prevented the antidepressant effect produced by MS in FST. However, pre-treatment of mice with metergoline (5-HT2 receptor antagonist, 4 mg/kg, i.p.) and yohimbine (α2-adrenoceptor antagonist, 1 mg/kg, i.p.) did not prevent the antidepressant effect of MS. In the EPM test, MS did not significantly increase open arm exploration. It also did not significantly increase the number of head dips in the hole-board test. Conclusions Results showed that MS had antidepressant activity possibly mediated through α1-adrenergic and D2 dopaminergic receptors, without significant anxiolytic effect.

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Methamphetamine Self-Administration: Neurochemical Consequences and Behavioural Effects

10.26686/wgtn.16997890.v1 ◽

2021 ◽

Author(s):

◽

Caleb Carati

Keyword(s):

Receptor Antagonist ◽

Receptor Agonist ◽

Sch 23390 ◽

High Dose ◽

Gbr 12909 ◽

Self Administration ◽

Drug Seeking ◽

Skf 81297 ◽

Pre Treatment

It has been suggested that methamphetamine (MA) self-administration is dependent on dopaminergic mechanisms, and that exposure to high doses of methamphetamine is toxic to central dopamine (DA) and serotonin (5-HT) neurons. Most studies, however, have utilised a short duration, high dose, experimenter-administered MA exposure regime, which is not representative of exposure that results from MA use in humans. The present studies sought to investigate the effects of self-administered MA on brain monoamine levels following a short and longer withdrawal period, and to determine the role of D1- and D2-like receptors in the maintenance of MA self-administration and in relapse to MA-seeking. The effects of self-administered MA (0.1 mg/kg/infusion) on tissue monoamine levels were determined in rats either 24 hours or seven days following 20 daily six hour sessions. A yoked-control self-administration protocol was employed to determine the effects of response contingency. The effect of pre-treatment with the D1-like receptor antagonist, SCH 23390 (0.0; 0.01; 0.02 mg/kg; subcutaneous [SC]), or the D2-like receptor antagonist, eticlopride (0.0; 0.0125; 0.025; 0.05 mg/kg; intraperitoneal [IP]) on MA self-administration reinforced according to a fixed ratio (FR) 1, and progressive ratio (PR; 0.2 mg/kg MA) schedule was determined. The effect of these pharmacological manipulations on relapse to MA-seeking was also determined. Additionally, the role of DA in drug-seeking was examined by measuring the effect of priming injections of the direct D1 receptor agonist, SKF 81297 (0.0; 1.0; 2.0; 4.0 mg/kg; IP), the direct D2 receptor agonist, quinpirole (0.0; 1.0 mg/kg; IP), or the DA transporter (DAT) inhibitor, GBR 12909 (0.0; 1.0; 10.0 mg/kg; IP), on MA-seeking behaviour. Self-administered MA produced a transient decrease in tissue levels of DA and an increase in DA turnover. This effect was produced at 24 hours, but not seven days following the final self-administration session. Similar effects were produced in yoked rats that received the same, non-contingent exposure to MA. Pre-treatment with SCH 23390, but not eticlopride, produced a significant alteration in the dose-response curve of MA self-administration reinforced on an FR1 schedule, and reduced MA produced BPs on the PR schedule. MA-seeking was produced by MA, cocaine and GBR 12909. SCH 23390 pre-treatment significantly reduced drug-primed MA-seeking, whereas eticlopride had no significant effect. Finally, neither SKF 81297, nor quinpirole significantly increased MA-seeking. These findings suggest that self-administered MA does not produce the extensive neurotoxicity seen following high-dose experimenter-administered treatment regimes. The finding that pre-treatment with a D1-, but not a D2-like receptor antagonist altered the maintenance of MA self-administration suggests that neuroadaptations take place as a function of MA self-administration, rendering this behaviour more reliant on D1-like receptor mechanisms. This idea is further supported by the finding that a D1-, but not a D2-like antagonist reduced drug-primed MA-seeking, and that priming injections with a D2 agonist failed to increase MA-seeking behaviour. These results are in contrast to the literature on self-administration and reinstatement of drug-seeking following self-administration of other drugs of abuse, and suggest that dependence on different drugs may become mediated by different DA receptor mechanisms.

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Methamphetamine Self-Administration: Neurochemical Consequences and Behavioural Effects

10.26686/wgtn.16997890 ◽

2021 ◽

Author(s):

◽

Caleb Carati

Keyword(s):

Receptor Antagonist ◽

Receptor Agonist ◽

Sch 23390 ◽

High Dose ◽

Gbr 12909 ◽

Self Administration ◽

Drug Seeking ◽

Skf 81297 ◽

Pre Treatment

It has been suggested that methamphetamine (MA) self-administration is dependent on dopaminergic mechanisms, and that exposure to high doses of methamphetamine is toxic to central dopamine (DA) and serotonin (5-HT) neurons. Most studies, however, have utilised a short duration, high dose, experimenter-administered MA exposure regime, which is not representative of exposure that results from MA use in humans. The present studies sought to investigate the effects of self-administered MA on brain monoamine levels following a short and longer withdrawal period, and to determine the role of D1- and D2-like receptors in the maintenance of MA self-administration and in relapse to MA-seeking. The effects of self-administered MA (0.1 mg/kg/infusion) on tissue monoamine levels were determined in rats either 24 hours or seven days following 20 daily six hour sessions. A yoked-control self-administration protocol was employed to determine the effects of response contingency. The effect of pre-treatment with the D1-like receptor antagonist, SCH 23390 (0.0; 0.01; 0.02 mg/kg; subcutaneous [SC]), or the D2-like receptor antagonist, eticlopride (0.0; 0.0125; 0.025; 0.05 mg/kg; intraperitoneal [IP]) on MA self-administration reinforced according to a fixed ratio (FR) 1, and progressive ratio (PR; 0.2 mg/kg MA) schedule was determined. The effect of these pharmacological manipulations on relapse to MA-seeking was also determined. Additionally, the role of DA in drug-seeking was examined by measuring the effect of priming injections of the direct D1 receptor agonist, SKF 81297 (0.0; 1.0; 2.0; 4.0 mg/kg; IP), the direct D2 receptor agonist, quinpirole (0.0; 1.0 mg/kg; IP), or the DA transporter (DAT) inhibitor, GBR 12909 (0.0; 1.0; 10.0 mg/kg; IP), on MA-seeking behaviour. Self-administered MA produced a transient decrease in tissue levels of DA and an increase in DA turnover. This effect was produced at 24 hours, but not seven days following the final self-administration session. Similar effects were produced in yoked rats that received the same, non-contingent exposure to MA. Pre-treatment with SCH 23390, but not eticlopride, produced a significant alteration in the dose-response curve of MA self-administration reinforced on an FR1 schedule, and reduced MA produced BPs on the PR schedule. MA-seeking was produced by MA, cocaine and GBR 12909. SCH 23390 pre-treatment significantly reduced drug-primed MA-seeking, whereas eticlopride had no significant effect. Finally, neither SKF 81297, nor quinpirole significantly increased MA-seeking. These findings suggest that self-administered MA does not produce the extensive neurotoxicity seen following high-dose experimenter-administered treatment regimes. The finding that pre-treatment with a D1-, but not a D2-like receptor antagonist altered the maintenance of MA self-administration suggests that neuroadaptations take place as a function of MA self-administration, rendering this behaviour more reliant on D1-like receptor mechanisms. This idea is further supported by the finding that a D1-, but not a D2-like antagonist reduced drug-primed MA-seeking, and that priming injections with a D2 agonist failed to increase MA-seeking behaviour. These results are in contrast to the literature on self-administration and reinstatement of drug-seeking following self-administration of other drugs of abuse, and suggest that dependence on different drugs may become mediated by different DA receptor mechanisms.

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Evidence for improved performance in cognitive tasks following selective NR2B NMDA receptor antagonist pre-treatment in the rat

Psychopharmacology ◽

10.1007/s00213-005-2203-9 ◽

2005 ◽

Vol 179 (1) ◽

pp. 85-98 ◽

Cited By ~ 54

Author(s):

Guy A. Higgins ◽

Theresa M. Ballard ◽

Michel Enderlin ◽

Marie Haman ◽

John A. Kemp

Keyword(s):

Nmda Receptor ◽

Receptor Antagonist ◽

Nmda Receptor Antagonist ◽

Cognitive Tasks ◽

Improved Performance ◽

Pre Treatment

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The effect of memantine on behavioural sensitisation to methamphetamine in mice

Veterinární Medicína ◽

10.17221/6366-vetmed ◽

2012 ◽

Vol 57 (No. 10) ◽

pp. 543-550 ◽

Cited By ~ 2

Author(s):

L. Landa ◽

K. Slais ◽

A. Sulcova

Keyword(s):

Nmda Receptor ◽

Receptor Antagonist ◽

Repeated Administration ◽

Nmda Receptor Antagonist ◽

Behavioural Sensitisation ◽

Inward Currents ◽

Nmda Glutamate Receptor ◽

Psychotropic Effects ◽

Pre Treatment ◽

Nmda Glutamate Receptor Antagonist

After repeated administration the psychostimulant methamphetamine (Met) produces a substantial increase in behavioural responses, which is termed behavioural sensitisation. Many studies have reported that N-methyl-d-aspartate (NMDA) receptors play an important role in the development and expression of behavioural sensitisation. Memantine (Mem) is used particularly for the treatment of Alzheimer’s disease and acts as a non-competitive NMDA glutamate receptor antagonist, possessing a variety of psychotropic effects. For example, there are studies indicating that memantine prevents the expression of withdrawal symptoms in mice and causes reversal of opioid dependence. Although not all pharmacological mechanisms of memantine have been clarified yet, it is known that memantine inhibits NMDA receptor inward currents. Thus, the present study was designed to assess whether memantine would influence behavioural sensitisation to the stimulatory effects of methamphetamine on mouse locomotion. Mice were randomly allocated into four groups. They were given vehicle on Day 1of the experiment and after five days without application they were administered seven drug daily doses (i.p.) from Day 7 to Day 13 of the study, as follows: (a) n1, 2: 2.5 mg/kg/day of Met; (b) n3: combination Met + Mem at the doses of 2.5 mg/kg/day and 5 mg/kg/day, respectively; (c) n4: Mem at the dose of 5 mg/kg/day. On Day 14 mice were given the first “challenge treatment” (a) n1: Met, (b) n2: Met + Mem, (c) n3: Met, (d) n4: Mem. The second “challenge treatment” was given after a six day wash-out period on Day 21: (a) n1: Met, (b) n2: Met + Mem, (c) n3: Met, (d) n4: Mem. Changes in locomotion were measured for a period of 3 min in the Open field on Days 1, 7, 14 and 21 to assess the sensitising phenomenon. Met pre-treatment significantly sensitised to the effects of the challenge doses (n1). Mem given alone did not change the measured behavioural parameters after the acute dose but it significantly decreased locomotion after its repeated administration (n4). Repeated pre-treatment with the Met + Mem combination (n3) did not produce sensitisation after Met challenge doses and similarly, repeated pre-treatment with Met did not induce sensitisation after the challenge dose of Met + Mem (n2). Thus, our results suggest that the role of the NMDA receptor antagonist memantine in the development and expression of behavioural sensitisation to Met seems to be an inhibitory one.

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