scholarly journals AMN 082, an agonist of mGluR7, exhibits mixed anti- and proconvulsant effects in developing rats

2008 ◽  
pp. 969-972
Author(s):  
P Mareš
Keyword(s):  
Metabotropic Glutamate Receptors ◽  
Age Groups ◽  
Adult Rats ◽  
Anticonvulsant Action ◽  
Metabotropic Glutamate ◽  
Old Rats ◽  
Clonic Seizures ◽  
Motor Effects ◽  
Tonic Phase ◽  
Observation Period

Metabotropic glutamate receptors (mGluRs) represent a potential therapeutic target. Possible anticonvulsant action of AMN 082, an agonist of mGluR7 subtype, was studied in immature rats using pentylenetetrazol (PTZ)-induced seizures as a model. Five age groups of rats (7-, 12-, 18-, 25-day-old and adult animals) were pretreated with AMN 082 in doses of 0.5, 1, 2, and 5 mg/kg i.p. and 30 min later PTZ was administered (100 mg/kg s.c.). Controls received saline instead of the agonist. AMN 082 did not exhibit clear anticonvulsant action with the exception of suppression of the tonic phase of generalized tonic-clonic seizures (GTCS) in 12-day-old rats. Shorter latencies of GTCS after AMN 082 pretreatment indicate a proconvulsant action. Involuntary movements (mostly tremor) appeared after AMN 082 before PTZ administration, therefore we performed another experimental series with AMN 082 only (1, 2, 5, and 10 mg/kg i.p.). During 60-min observation period tremor appeared in all age groups; sensitivity to this action decreased with age from the 2 mg/kg dose in 7- and 12-day-old rats to the 10 mg/kg dose in adult rats. Mixed anti- and proconvulsant actions of AMN 082 together with unwanted motor effects makes clinical use of this drug highly improbable.

scholarly journals Anticonvulsant action of GABA-B receptor agonist SKF97541 differs from that of Baclofen

2008 ◽  
pp. 789-792
Author(s):  
P Mareš
Keyword(s):  
Receptor Agonist ◽  
Age Groups ◽  
Mixed Effects ◽  
Adult Rats ◽  
Anticonvulsant Action ◽  
Generalized Seizures ◽  
Age Dependent ◽  
Old Rats ◽  
Clonic Seizures ◽  
Tonic Phase

GABA-B receptor agonist SKF97541 exhibits age-dependent anticonvulsant and proconvulsant actions in developing rats. It suppressed tonic phase of generalized seizures induced by pentetrazol in 7-, 12- and 18-day-old rats and increased their latency in 7- and 12-day-old animals. Other results in 18-day-old animals are not so clear. SKF97541 blocked the appearance of minimal clonic seizures, but tended to decrease latencies of both types of seizures. In addition, it significantly decreases latency of generalized seizures in adult rats. The mixed effects of SKF97541 are in agreement with those of baclofen but there are substantial differences between the actions of these two agonists in individual age groups.

scholarly journals Anticonvulsant Action of a New Analogue of Allopregnanolone in Immature Rats

2010 ◽  
pp. 305-308
Author(s):  
P Mareš ◽  
H Kubová ◽  
A Kasal
Keyword(s):  
Clinical Trials ◽  
Acute Treatment ◽  
Age Groups ◽  
Neuroactive Steroid ◽  
Reference Drug ◽  
Anticonvulsant Action ◽  
Immature Rats ◽  
Effective Doses ◽  
Old Rats ◽  
Clonic Seizures

Neuroactive steroids represent potential antiepileptic drugs. We tested a newly synthesized analogue of allopregnanolone 3αhydroxy-21ξ,22-oxido-21-homo-5α-pregnan-20-on (HOHP) against two types of pentylenetetrazol-induced seizures (100 mg/kg s.c.) in 12- and 25-day-old rats. Ganaxolone, a neuroactive steroid in clinical trials, served as a reference drug. Pretreatment with either steroid suppressed generalized tonicclonic seizures in both age groups, their efficacy was comparable. HOHP as well as ganaxolone were more active in 12- than in 25-day-old rats (effective doses were 40 and 60 mg/kg, respectively). Minimal clonic seizures, which can be elicited only in 25-day-old rats, were not influenced by any drug. Very short duration of anticonvulsant action of HPOP demonstrated in 12-day-old animals indicates that this drug might be used only in acute treatment in epileptology.

scholarly journals What is the role of neurotransmitter systems in cortical seizures?

2008 ◽  
pp. S111-S120
Author(s):  
P Mareš ◽  
H Kubová
Keyword(s):  
Glutamate Receptors ◽  
Metabotropic Glutamate Receptors ◽  
Gabab Receptor ◽  
Age Groups ◽  
Gabab Receptors ◽  
Neurotransmitter Systems ◽  
Metabotropic Glutamate ◽  
Rat Pups ◽  
Epileptic Afterdischarges

Epileptic afterdischarges (ADs) elicited by electrical stimulation of sensorimotor cortical area were used as a model to study the role of neurotransmitter systems in cortical seizures in three age groups of developing rats. Drugs augmenting inhibition mediated by GABAA receptors were found to suppress ADs in all age groups, their activity was usually more marked in younger than in 25-day-old rat pups. Drugs potentiating GABAB receptors exhibit lower efficacy and more complicated developmental profile than GABAA-ergic drugs. Effects of an antagonist of GABAB receptor--marked prolongation of ADs in all three age groups--suggest an important role of GABAB receptors in arrest of cortical seizures. Drugs affecting glutamate receptors exhibit variable effects, usually better expressed in older animals than in 12-day-old ones. No specific role for ionotropic as well as metabotropic glutamate receptors could be predicted. Activation of adenosinergic inhibitory modulatory system also exhibited anticonvulsant action in the present model. All three neurotransmitter systems probably participate in mechanisms of generation, maintenance and arrest of cortical seizures.

Sensitivity of lungs of aging Fischer 344 rats to ozone: assessment by bronchoalveolar lavage

1996 ◽  
Vol 271 (4) ◽  
pp. L555-L565 ◽  
Author(s):  
R. Vincent ◽  
D. Vu ◽  
G. Hatch ◽  
R. Poon ◽  
K. Dreher ◽  
...  
Keyword(s):  
Bronchoalveolar Lavage ◽  
Biological Effects ◽  
Age Groups ◽  
Lavage Fluid ◽  
Lung Lavage ◽  
Ozone Exposure ◽  
Fischer 344 Rats ◽  
Adult Rats ◽  
Fischer 344 ◽  
Old Rats

Biological effects indicators in bronchoalveolar lavage fluid were studied in Fischer 344 rats of different ages after exposure to 0.4-0.8 ppm ozone for periods of 2-6 h on a single day or on 4 consecutive days. The magnitude of alveolar protein transudation induced by ozone was not different between age groups, but the interindividual variability of protein changes was higher in senescent (24-mo-old) rats. By comparison to juvenile (2-mo-old) and adult (9-mo-old) rats, senescent animals had higher increases of interleukin-6 (up to 10-fold higher) and N-acetyl-beta-D-glucosaminidase (NAGA; 2-fold higher) in lung lavage after ozone. Ascorbic acid was lower in lungs of senescent rats (one-half of juvenile values), and acute ozone exposure brought a further decrease in lung ascorbate. Whereas alveolar protein transudation was attenuated after ozone exposure on 4 days, persistent elevation of NAGA in senescent rats suggested only partial adaptation. Injection of endotoxin did not modify the patterns of effects. Incorporation of 18O-ozone into macrophages and surfactant was not different between age groups, indicating that the magnified biological responses in senescent rats were not dominated by differences in internal dose of ozone. The results indicate that senescent rats respond differently than juvenile and adult rats to lung injury.

scholarly journals Morphological and biochemical studies on the development of cholinergic properties in cultured sympathetic neurons. II. Dependence on postnatal age.

1980 ◽  
Vol 84 (3) ◽  
pp. 692-704 ◽  
Author(s):  
M I Johnson ◽  
C D Ross ◽  
R P Bunge
Keyword(s):  
Synaptic Vesicle ◽  
Neuronal Development ◽  
Specific Activity ◽  
Sympathetic Neurons ◽  
Age Groups ◽  
Adult Rats ◽  
Old Rats ◽  
Cultured Sympathetic Neurons ◽  
Neurotransmitter Plasticity

Superior cervical ganglion (SCG) neurons taken from perinatal rats and dissociated in culture develop cholinergic properties. This report examines this "plasticity" of neurotransmitter function with regard to its dependence on the stage of neuronal development. Explants of SCG from rats ranging in age from 2 d to adult were cultured, and the number of neurons surviving after 6 wk in culture was evaluated. The activities of choline acetyltransferase (ChAc) and DOPA decarboxylase (DDC) were assayed for each age group over time in culture, and the cytochemistry of the synaptic vesicle population was studied after norepinephrine loading and KMnO4 fixation. The specific activity of ChAc in all explants fell during the first 3--4 d in culture (secondary to degeneration of presynaptic terminals), with an increase during the next 30 d in explants from all age groups except in those from the 22-d-old and adult rats. The highest activity found after 1 mo in culture was in explants from 2-d-old rats (62.5 mmol per kg dry wt per h); the lowest was in explants from adults (1.3 nmol per kg dry wt per h). After 1 mo in vitro, there were no significant differences in DDC activity among explants from animals of any age (similar to approximately 220 mmol per kg dry wt per h). Co-culture of the SCG explants with heart muscle increased even further the ChAc activity in explants from 2-d-old rats but not in explants from 16-d-old and 6.5-wk-old animals. The cytochemistry of the synaptic vesicle population in 1-mo-old cultures correlated well with the ChAc activity; when the ChAc activity was high, the proportion of synaptic vesicles with clear centers was 71--88%. In explants from adult animals, only 12% of the vesicles contained clear centers. From these data we conclude that the maturity of the SCG neuron influences the degree to which it is able to adjust its neurotransmitter mechanisms. That the axons of this neuron are interacting with target tissues during the time that neurotransmitter plasticity is retained suggests that interaction with the target may play a role in the determination of transmitter type.

Differential Changes of Group II and Group III mGluR Function in Central Amygdala Neurons in a Model of Arthritic Pain

2006 ◽  
Vol 96 (4) ◽  
pp. 1803-1815 ◽  
Author(s):  
Weidong Li ◽  
Volker Neugebauer
Keyword(s):  
Metabotropic Glutamate Receptors ◽  
Central Nucleus ◽  
Noxious Stimulation ◽  
Adult Rats ◽  
Group Iii ◽  
Metabotropic Glutamate ◽  
Group I ◽  
Group Ii ◽  
Joint Arthritis ◽  
Stimulation Of

Metabotropic glutamate receptors (mGluRs) play important roles in neuroplasticity and disorders such as persistent pain. Group I mGluRs contribute to pain-related sensitization and synaptic plasticity of neurons in the laterocapsular division of the central nucleus of the amygdala (CeLC), although the roles of groups II and III mGluRs are not known. Extracellular single-unit recordings were made from 60 CeLC neurons in anesthetized adult rats. Background activity and evoked responses were measured before and during the development of the kaolin/carrageenan-induced knee-joint arthritis. Drugs were administered into the CeLC by microdialysis before and/or after arthritis induction. A selective group III mGluR agonist (LAP4) inhibited CeLC neurons' responses to stimulation of the knee and ankle in arthritis ( n = 7) more potently than under normal conditions ( n = 14). A selective group II agonist (LY354740) inhibited responses under normal conditions ( n = 12) and became more potent in inhibiting responses to noxious stimulation of the knee in arthritis ( n = 10). The effect of LY354740 on innocuous stimulation of the knee and stimulation of the ankle did not change in arthritis. Antagonists for groups II (EGLU, n = 9) and III (UBP1112, n = 8) had no effects under normal conditions. In arthritis, UPB1112 ( n = 5) facilitated the responses to stimulation of knee and ankle, whereas EGLU ( n = 5) selectively increased the responses to stimulation of the knee. These data suggest that mGluRs of groups II and III can inhibit nociceptive processing in CeLC neurons. The increased function and endogenous activation of group II mGluRs in the arthritis pain model appear more input-selective than the general changes of group III mGluRs.

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