6 research outputs found
Anticonvulsant effect of minocycline on pentylenetetrazole-induced seizure in mice: involvement of nitric oxide and N-methyl-D-aspartate receptor
Anticonvulsant effects of minocycline have been explored recently. This study was designed to examine the anticonvulsant
effect of acute administration of minocycline on pentylenetetrazole-induced seizures in mouse considering the possible role of the
nitric oxide/N-methyl-D-aspartate (NMDA) pathway. We induced seizure using intravenous administration of pentylenetetrazole. Our
results showed that acute administration of minocycline increased the seizure threshold. Furthermore, co-administration of subeffective
doses of the nonselective nitric oxide synthase (NOS) inhibitor NG-L-arginine methyl ester (10 mg/kg) and the neuronal NOS
inhibitor 7-nitroindazole (40 mg/kg) enhanced the anticonvulsant effect of subeffective doses of minocycline (40 mg/kg). We found
that inducible NOS inhibitor aminoguanidine (100 mg/kg) had no effect on the antiseizure effect of minocycline. Moreover, L-arginine
(60 mg/kg), as a NOS substrate, reduced the anticonvulsant effect of minocycline. We also demonstrated that pretreatment with the
NMDAreceptor antagonists ketamine (0.5 mg/kg) and MK-801 (0.05 mg/kg) increased the anticonvulsant effect of subeffective doses of
minocycline. Results showed that minocycline significantly decreased the hippocampal nitrite level. Furthermore, co-administration
of a neuronal NOS inhibitor like NMDA receptor antagonists augmented the effect of minocycline on the hippocampal nitrite level.
In conclusion, we revealed that anticonvulsant effect of minocycline might be, at least in part, due to a decline in constitutive
hippocampal nitric oxide activity as well as inhibition of NMDA receptors
NMDA receptor antagonists attenuate the proconvulsant effect of juvenile social isolation in male mice
Experiencing psychosocial stress inearly life, suchas social isolationstress (SIS), is knowntohavenegative
enduring effects on the development of the brain and behavior. In addition to anxiety and depressive-like
behaviors, we previously showed that juvenile SIS increases susceptibility to pentylenetetrazole (PTZ)-
induced seizures in mice through enhancing the nitrergic system activity in the hippocampus. In this
study, we investigated the possible involvement of N-methyl-d-aspartate (NMDA) receptors in proconvulsant
effects of juvenile SIS. Applying 4 weeks of SIS to juvenile male mice at postnatal day 21–23, we
observed an increased susceptibility to PTZ as well as anxiety and depressive-like behaviors in adult mice.
Intraperitoneal (i.p.) administration of NMDA receptor antagonists, MK-801 (0.05 mg/kg) and ketamine
(0.5 mg/kg), reversed the proconvulsant effects of SIS in Isolated (and not social) housed animals. Coadministration
of non-effective doses of nitric oxide synthase (NOS) inhibitors, 7NI (25 mg/kg) and
L-NAME (10 mg/kg), with NMDA receptor antagonists, MK-801 (0.01 mg/kg) and ketamine (0.1 mg/kg)
attenuated the proconvulsant effects of juvenile SIS only in isolated housed mice. Also, using real time
RT-PCR, we showed that hippocampal upregulation of NR2B subunit of NMDA receptor may play a critical
role in proconvulsant effects of juvenile SIS by dysregulation of NMDA/NO pathway. In conclusion,
results of present study revealed that experiencing SIS during adolescence predisposes the co-occurrence
of seizure disorders with psychiatric comorbidities and also, alteration of NMDA receptor structure and
function in hippocampus plays a role in proconvulsant effects of juvenile SIS through enhancing the
NMDA/NO pathwa
Experiencing neonatal maternal separation increased the seizure threshold in adult male mice: Involvement of the opioid system
Experiencing early-life stress has been considered as a potent risk factor for the development of many of brain
disorders, including seizures. Intervening mechanisms through which neonatal maternal separation (MS) alters
the seizure susceptibility in adulthood have not been well studied. In the current study, by applying 180 min of
MS stress (PND 2–14), we determined the seizure susceptibility and considered the role of the opioid system.
Maternal separation increased the seizure threshold, and administration of anticonvulsant/proconvulsant
doses of morphine (1 and 30 mg/kg, respectively) reversed the impact of MS. Using tail flick and hot plate
tests, we exposed animals to 30 min Restraint stress (RS) and found that MS decreased the pain threshold,
suggesting the hyporesponsiveness of the opioid system. These results supported the abnormal seizure activity
observed in the MS mice and suggested that abnormalities in the opioid system following MS alter seizure
susceptibility in later life
Protective effects of gabapentin against the seizure susceptibility and comorbid behavioral abnormalities in the early socially isolated mice
Adolescence is a pivotal period of brain development during lifespan, which is sensitive to stress exposure. Early social isolation stress (SIS) is known to provoke a variety of psychiatric comorbidities as well as seizure risk. Psychiatric comorbidities present challenging dilemmas for treatment and management in people with seizure disorders. In this study, we aimed to investigate whether gabapentin (GBP) as an anti-epileptic drug is able to alleviate the seizure activity as well as comorbid behavioral abnormalities in socially isolated mice. Results showed that early SIS induced proconvulsant effects along with depressive, aggressive and anxiety-like behaviors. Whereas the administration of both acute and chronic GBP at sub-effective doses produced no alterations in the behavioral profile of socially conditioned counterparts the same treatments effectively reversed the seizure susceptibility to pentylenetetrazole and behavioral deficits in isolated mice. Results of the study indicate that 1) Early SIS could be considered as an animal model of psychosocial stress to investigate the psychiatric comorbidities in seizure disorders, 2) Chronic administration of low dose GBP prevented the shaping of behavioral abnormalities in adulthood, 3) Chronic administration of low dose GBP produced no negative behavioral effects in socially conditioned mice suggesting the safety of the drug, 4) Gabapentin at low doses may be considered as an agent for management of epilepsy in individuals with psychiatric comorbidities
Morphine modulates the effects of histamine H1 and H3 receptors on seizure susceptibility in pentylenetetrazole-induced seizure model of mice
Histamine regulates release of neurotransmitters such as dopamine, serotonin, gamma-aminobutyric
acid (GABA), glutamate and also is involved in several functions in central nervous system (CNS). It has
been shown that histamine participates in disorders like seizure. It has been well documented that
morphine dose-dependently induces anti or proconvulsant effects. In the current study, we firstly
showed that morphine (1 mg/kg) exerts anticonvulsant effects which significantly reversed by naltrexone
administration. Secondly, we determined seizure threshold for H1 and H3 receptors agonists and
antagonists in mouse model of pentylenetetrazole (PTZ)-induced clonic seizures. Our results showed that
activation of H1 receptors by 2-(2-Pyridyl)-ethylamine exerts anticonvulsant properties while inhibition
of H1 receptors by pyrilamine maleate induced proconvulsant effects. Furthermore, we showed that
immepip dihydrobromide, a H3 receptor agonist, increased seizure susceptibility to PTZ whereas thioperamide,
a H3 receptor antagonist increased seizure threshold. We also revealed that pretreatment with
morphine potently reversed the effects of histaminergic system on seizure threshold suggesting the
involvement of opioid system in alteration of seizure threshold by histaminergic drug
Lithium attenuates the proconvulsant effect of adolescent social isolation stress via involvement of the nitrergic system
In this study, we tested whether acute administration of lithium mitigates the deleterious effect of adolescent social
isolation stress (SIS) on seizure susceptibility. In comparison with socially conditioned (SC) mice, isolated
conditioned (IC) mice exhibited an increase in seizure susceptibility to pentylenetetrazole. Acute administration
of lithium (10 mg/kg) reversed the proconvulsant effect of SIS in IC mice, but this effect was not observed in SC
mice. Coadministration of subthreshold doses of lithium (3 mg/kg) with nitric oxide synthase (NOS) inhibitors
reversed the effect of SIS on seizure susceptibility and decreased hippocampal nitrite levels in IC animals. In
addition, a subthreshold dose of a nitric oxide precursor reduced the protective effect of lithium on seizure susceptibility
and increased nitrite levels in the hippocampus of IC mice. These results suggest that lithium exerts a
protective influence against the proconvulsant effect of adolescent SIS via a nitrergic system that includes activation
of neuronal NOS in the hippocampus