scholarly journals Proconvulsant Action of Two GABAB Receptor Antagonists Is Age-Dependent

2013 ◽  
pp. S109-S114 ◽  
Author(s):  
P. MAREŠ
Keyword(s):  
Gabab Receptor ◽  
Water Soluble ◽  
Gabab Receptors ◽  
Implanted Electrodes ◽  
Rat Pups ◽  
Age Dependent ◽  
Old Rats ◽  
Gabab Receptor Antagonists ◽  
Epileptic Afterdischarges

Antagonists of GABAB receptors are expected to have proconvulsant action also in developing brain. Two antagonists (CGP55845 and CGP46381) were tested in a model of cortical epileptic afterdischarges (ADs) in 12-, 18- and 25-day-old rat pups with implanted electrodes. CGP55845 was dissolved in dimethylsulfoxide and the results demonstrated marked proconvulsant action of this solvent which masked possible action of the antagonist. Water soluble antagonist CGP46381 led to marked potentiation of ADs in 12-day-old animals, its action decreased with age, it was negligible in 25-day-old rats. Our results demonstrated important inhibitory role of GABAB receptors at very early stages of maturation.

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.

The role of GABA-mediated inhibition in the rat ventral posterior medial thalamus. II. Differential effects of GABAA and GABAB receptor antagonists on responses of VPM neurons

1994 ◽  
Vol 71 (5) ◽  
pp. 1716-1726 ◽  
Author(s):  
S. M. Lee ◽  
M. H. Friedberg ◽  
F. F. Ebner
Keyword(s):  
Receptive Field ◽  
Gabab Receptor ◽  
Response Duration ◽  
Fold Increase ◽  
Gamma Aminobutyric Acid ◽  
Recording Conditions ◽  
Peripheral Areas ◽  
Gabab Receptor Antagonists ◽  
Spontaneous Firing Rate

1. Changes in the response properties of 106 ventral posterior medial (VPM) units were assessed after iontophoretic blockade of gamma-aminobutyric acid-A or -B (GABAA or GABAB) receptor-mediated inhibition using bicuculline methiodide (BIC) or 2-hydroxy-saclofen (2-OH-S), respectively. 2. The iontophoretic administration of either BIC or 2-OH-S did not alter significantly the average spontaneous firing rate of VPM neurons for current intensities between 40 and 80 nA. The presence of 10 mM 2-OH-S (60 nA) was effective in completely reversing the depressant effects of the selective GABAB receptor agonist, baclofen, on the spontaneous activity of VPM neurons. 3. The effect of BIC on whisker-evoked responses was a preferential enhancement in the responses elicited by the whisker giving rise to the highest probability response (center receptive field whisker or CRF). The effect of 2-OH-S (40-80 nA iontophoretic currents) was to increase the responsiveness of VPM neurons to the stimulation of whiskers in all parts of the receptive field (RF), although its influence was much more pronounced in the peripheral areas of the RF (surround receptive field whisker or SRF). This preferential enhancement of SRF-whisker responses after the blockade of GABAB receptor-mediated inhibition resulted in a 2.3-fold increase in the average RF size of VPM neurons; no statistically significant increases in the size of the RF were seen in the presence of BIC. 4. The primary influence of BIC and, to a lesser degree, 2-OH-S was to prolong the response duration of VPM neurons to CRF whisker stimulation. Under our recording conditions, approximately 25% of VPM neurons in normal animals responded with sustained discharges. In the presence of BIC and 2-OH-S, the percent of VPM units that could be classified as tonically responding increased to 82% and 67%, respectively. 5. The proportion of VPM neurons that was selective to the deflection of whiskers in a particular direction (87%) was not altered in the presence of BIC or 2-OH-S. 6. BIC was effective in antagonizing GABA-mediated inhibition within the first 40 ms of a stimulus; BIC was completely ineffective in reversing a late suppression seen between 80 and 140 ms. In contrast, no statistically significant changes in the initial GABA-mediated inhibition were seen in the presence of 2-OH-S, but 2-OH-S was partially effective in antagonizing the late suppression of responses in VPM neurons.(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals Transient Changes of Cortical Interhemispheric Responses After Repeated Caffeine Administration in Immature Rats

2011 ◽  
pp. 961-969 ◽  
Author(s):  
J. TCHEKALAROVA ◽  
H. KUBOVÁ ◽  
P. MAREŠ
Keyword(s):  
Developmental Changes ◽  
Adult Rats ◽  
Frequency Responses ◽  
Transient Nature ◽  
Rat Pups ◽  
Wistar Strain ◽  
Opposite Change ◽  
Frequency Stimulation ◽  
Old Rats ◽  
Epileptic Afterdischarges

Repeated postnatal caffeine treatment of rat pups led to transient developmental changes in cortical epileptic afterdischarges. To know if physiological cortical functions are also affected transcallosal evoked potentials were studied. Rat pups of the Wistar strain were injected daily with caffeine (10 or 20 mg/kg s.c.) from postnatal day (P) 7 to P11, control siblings received saline. Cortical interhemispheric responses were tested at P12, 18, 25 and in young adult rats. Amplitude of initial monosynaptic components was evaluated in averaged responses. Single pulses as well as paired and frequency (five pulses) stimulations were used. Developmental rules – highest amplitude of responses in 25-day-old rats, potentiation with paired and frequency stimulation present since P18 – were confirmed. Caffeine-treated rats exhibited transient changes: single responses were augmented in P25 if high stimulation intensity was used, paired-pulse and frequency responses were higher in experimental than in control animals at P12, the opposite change was observed in 18- and more markedly in 25-day-old rats. No significant changes were found in adult animals, monosynaptic transcallosal responses represent a simple and robust system. The developmental profile of described changes did not exactly correspond to changes in epileptic afterdischarges supporting the possibility that afterdischarges did not arise from early monosynaptic components of responses. In spite of transient nature of changes they can reflect delayed or more probably modified brain development.

Age-dependent biliary excretion of glutathione-related thiols in rats: role of gamma-glutamyltransferase

1987 ◽  
Vol 253 (1) ◽  
pp. G86-G92 ◽  
Author(s):  
Z. Gregus ◽  
A. F. Stein ◽  
C. D. Klaassen
Keyword(s):  
Postnatal Development ◽  
Biliary Excretion ◽  
Excretion Rate ◽  
Dependent Manner ◽  
Gamma Glutamyltransferase ◽  
Hydrolysis Products ◽  
Age Dependent ◽  
Old Rats ◽  
Hydrolysis Of

The role of gamma-glutamyltransferase (GGT) in the biliary excretion of glutathione (GS) was studied in rats during postnatal development. Between 2 and 10 wk of age the biliary excretion of GS-related sulfur increased ninefold. During this period, alterations were observed in both hepatic GGT and the composition of GS-related thiols and disulfides in bile. For instance, between 3 and 4 wk of age, GGT activity and the biliary excretion of GS hydrolysis products (Cys-Gly and Cys) increased markedly, and the latter became the predominant sulfhydryls in bile. However, by 10 wk of age, the excretion rate of GS increased and exceeded the rate of excretion of Cys-Gly and Cys. The parallelism between hepatic GGT activity and the biliary excretion of GS-hydrolysis products during development suggests a role for GGT in the formation of biliary Cys-Gly and Cys. Furthermore, in 4-wk-old rats, inhibition of hepatic GGT by acivicin markedly decreased the biliary excretion of Cys-Gly and Cys and increased that of GS without influencing the excretion of total GS-related sulfur in bile. The biliary excretion of GS-related thiols was less responsive to acivicin in 2- and 7- to 10-wk-old rats, suggesting that GGT plays a smaller role in influencing biliary thiol composition at those ages. In summary, GS transported into bile is hydrolyzed in an age-dependent manner, however, the GGT-initiated hydrolysis of GS does not affect the biliary excretion of total thiols in rats.

The role of N-cholinoreceptors in somatovisceral intersystemic interactions in early rat ontogenesis

2021 ◽  
Vol 19 (3) ◽  
pp. 303-312
Author(s):  
Vladimir A. Sizonov ◽  
Ludmila E. Dmitrieva ◽  
Sergey V. Kuznetsov
Keyword(s):  
Acetylcholinesterase Inhibitor ◽  
Wistar Rat ◽  
Internal Environment ◽  
Rat Pups ◽  
Cholinergic Regulation ◽  
Motor Activities ◽  
Intersystemic Interactions ◽  
Old Rats ◽  
Cholinergic Effects

Interaction of slow-wave rhythmic components of cardiac, respiratory and motor activities was analyzed in non-narcotized of newborn 1-day-old (P1) and 16-day-old (P16) Wistar rat pups under normal and impaired cholinergic regulation. Functional activity of these three systems is rhythmic, and coordination of their functioning is an important element of the mechanism of adaptive rearrangements under changing factors of the external and internal environment. The acetylcholinesterase inhibitor physostigmine (eserine) was used to increase the level of endogenous acetylcholine and enhance cholinergic effects. To reveal the role of N-cholinoreceptors in intersystemic somatovisceral interactions (ISI), we performed blockade of this receptor type with benzohexonium. Administration of physostigmine leads to the development of a number of pathological reactions and a decrease in the level of ISI in all ranges of modulating rhythms in rats of both ages. ISI in younger rats appear to be more resistant to changes in the level of cholinergic activation. Blockade of N-cholinoreceptors causes inhibition of ISI at P1 and partially to their potentialization at P16. The activation of cholinoreactive structures, which occurred against the background of cholinoreceptors blockade, reduces the pathological effects of physostigmine in animals of both ages, but at the same time leads to an attenuation of ISI. This weakening is more pronounced in 16-day old rats, which may indicate the formation of the definitive level of cholinergic regulation in the first weeks of postnatal ontogenesis.

Gabab Receptors: Are They Missing In Action In Focal Epilepsy Research?

2021 ◽  
Vol 19 ◽  
Author(s):  
Massimo Avoli ◽  
Maxime Lévesque
Keyword(s):  
Gabab Receptor ◽  
Focal Epilepsy ◽  
Second Messengers ◽  
Gabab Receptors ◽  
Receptor Function ◽  
Inhibitory Neurotransmitter ◽  
Epilepsy Research ◽  
Missing In Action

: GABA, the key inhibitory neurotransmitter in the adult forebrain, activates pre- and postsynaptic receptors that have been categorized as GABAA, which directly open ligand-gated (or receptor-operated) ion-channels, and GABAB, which are metabotropic since they operate through second messengers. Over the last three decades, several studies have addressed the role of GABAB receptors in the pathophysiology of generalized and focal epileptic disorders. Here, we will address their involvement in focal epileptic disorders by mainly reviewing in vitro studies that have shown: (i) how either enhancing or decreasing GABAB receptor function can favour epileptiform synchronization and thus ictogenesis, although with different features; (ii) the surprising ability of GABAB receptor antagonism to disclose ictal-like activity when excitatory ionotropic transmission is abolished; and (iii) their contribution to control seizure-like discharges during repetitive electrical stimuli delivered in limbic structures. In spite of this evidence, the role of GABAB receptor function in focal epileptic disorders has been attracting less interest when compared to the numerous studies that have addressed GABAA receptor signaling. Therefore, a main aim of our mini-review is to revive interest in the function of GABAB receptors in focal epilepsy research.

5α-Reductase activity regulates testosterone accumulation in two bands of immature cultured Leydig cells isolated on Percoll density gradients

1989 ◽  
Vol 121 (4) ◽  
pp. 538-544 ◽  
Author(s):  
Eisuke P. Murono ◽  
Amie L. Washburn
Keyword(s):  
Leydig Cells ◽  
Reductase Inhibitor ◽  
Reductase Activity ◽  
Band 3 ◽  
Density Gradients ◽  
Testosterone Levels ◽  
Age Dependent ◽  
Old Rats ◽  
Cells Cultured

Abstract. The 5α-reductase inhibitor, 4-methyl-4-aza-3-oxo-5α-pregnan-20(s)-carboxylate was utilitzed to examine maturational changes in testosterone synthesizing capacity of Leydig cells localizing in Band 2 and Band 3 of Percoll density gradients. Immature Band 2 Leydig cells (from 25- to 39-day-old rats) cultured without the 5α-reductase inhibitor, produced increased testosterone in response to hCG or 8-br-cAMP; however, basal, hCG- or 8-br-cAMP-stimulated testosterone accumulation was 4- to 12-fold higher when cells were cultured in the presence of inhibitor. Band 2 cells from older rats produced much less testosterone in response to hCG or 8-br-cAMP (<3.5 pmol/105), even when cultured with the inhibitor. Although immature Band 3 cells cultured in the absence of 5α-reductase inhibitor produced increased testosterone in response to hCG or 8-br-cAMP, testosterone levels were relatively low, because elevated 5α-reductase prevented appreciable androgen accumulation; however, Band 3 cells from older rats (over 39 days old) accumulated progressively more testosterone, because of the age-dependent decline in 5α-reductase activity. Immature Band 3 cells cultured with the 5α-reductase inhibitor accumulated 20- to 44-fold more testosterone in response to hCG of 8-br-cAMP. Thus, testosterone levels in control, hCG- or 8-br-cAMP-treated Band 3 cells form 39-day-old rats were 61.5, 177.2, and 500.3 pmol/105 cells, respectively. Testosterone declined from these high immature levels; however, testosterone still was relatively high in Band 3 cells of 63-day-old animals (83.4 and 98.3 pmol/105 cells in response to hCG or 8-br-cAMP, respectively). These studies demonstrate the viability of Leydig cells localizing in Band 2, emphasize the role of 5α-reductase activity in regulating testosterone accumulation of Leydig cells in both Band 2 and Band 3 and demonstrate differences in the pattern of testosterone production with maturation in cultured Leydig cells in Band 2 and Band 3.

scholarly journals Effect of GABAB Receptor Agonist SKF97541 on Cortical and Hippocampal Epileptic Afterdischarges

2014 ◽  
pp. 529-534 ◽  
Author(s):  
P. FÁBERA ◽  
P. MAREŠ
Keyword(s):  
Gabaa Receptors ◽  
Receptor Agonist ◽  
Gabab Receptor ◽  
Dorsal Hippocampus ◽  
Brain Structures ◽  
Gabab Receptors ◽  
Adult Rats ◽  
Inhibitory Postsynaptic Potentials ◽  
Male Wistar Rats ◽  
Epileptic Afterdischarges

Activation of GABAB receptors leads to longer inhibitory postsynaptic potentials than activation of GABAA receptors. Therefore GABAB receptors may be a target for anticonvulsant therapy. The present study examined possible effects of GABAB receptor agonist SKF97541 on cortical and hippocampal epileptic afterdischarges (ADs). Epileptic ADs elicited by electrical stimulation of sensorimotor cortex or dorsal hippocampus were studied in adult male Wistar rats. Stimulation series were applied 6 times with 10- or 20-min interval. Either interval was efficient for reliable elicitation of cortical ADs but stimulation at 10-min intervals did not reliably elicit hippocampal ADs, many stimulations were without effect. SKF97541 in dose 1 mg/kg significantly prolonged cortical ADs. Duration of hippocampal ADs was not significantly changed by either dose of SKF97541 in spite of a marked myorelaxant effect of the higher dose. Our present data demonstrated that neither cortical nor hippocampal ADs in adult rats were suppressed by GABAB receptor agonist SKF97541. Proconvulsant effect on cortical ADs indicates a different role in these two brain structures. In addition, duration of refractory period for electrically-induced ADs in these two structures in adult rats is different.

GABAB receptor-mediated mechanisms in the RVLM studied by microinjections of two GABAB receptor antagonists

1994 ◽  
Vol 266 (5) ◽  
pp. H1722-H1728 ◽  
Author(s):  
G. L. Avanzino ◽  
P. Ruggeri ◽  
D. Blanchi ◽  
C. E. Cogo ◽  
R. Ermirio ◽  
...  
Keyword(s):  
Gabab Receptor ◽  
Cardiovascular Effects ◽  
Gabab Receptors ◽  
Ventrolateral Medulla ◽  
Gamma Aminobutyric Acid ◽  
Inhibitory Mechanism ◽  
Electrolytic Lesions ◽  
Gabab Antagonists ◽  
Gabab Receptor Antagonists ◽  
Cgp 35348

The cardiovascular effects of microinjections of two gamma-aminobutyric acid (GABA) antagonists specifically acting on GABAB receptors, 2-hydroxy-saclofen (2-OH-S) and CGP-35348, into vasopressor sites of rostral ventrolateral medulla (RVLM) were studied in rats anesthetized with urethan. Bilateral microinjection of 2-OH-S induced significant increases in mean arterial pressure (MAP) and heart rate (HR) in 21 of 26 RVLM vasopressor sites (81%); average increases obtained in the 26 sites studied were +25.2 +/- 3.0 mmHg and +12.7 +/- 2.1 beats/min. Bilateral microinjection of CGP-35348 induced significant increases in MAP and HR in 10 of 12 RVLM sites (83%). Average increases in the 12 sites studied were +27.6 +/- 3.9 mmHg and +14.6 +/- 2.5 beats/min. Sixteen rats received unilateral electrolytic lesions of one RVLM. Microinjections of either 2-OH-S or CGP-35348 into vasopressor sites within the intact RVLM significantly antagonized the depressor responses observed after injections of baclofen (20 pmol) into the same sites, whereas both GABAB antagonists did not affect the depressor response induced by microinjection of muscimol (5 pmol). These results suggest a tonic inhibitory mechanism within the RVLM mediated by GABAB receptors involved in central cardiovascular regulation.

Neonatal and maternal prostaglandin in the ontogenic response of rat gastric mucosa to H+

1988 ◽  
Vol 254 (2) ◽  
pp. G142-G150
Author(s):  
C. E. Thorn ◽  
B. L. Tepperman
Keyword(s):  
Gastric Mucosa ◽  
Neonatal Rat ◽  
Rat Stomach ◽  
Maternal Milk ◽  
Rat Pups ◽  
Rat Gastric Mucosa ◽  
Endogenous Prostaglandins ◽  
Old Rats ◽  
Gastric Permeability

We have previously demonstrated that neonatal rat stomach is less susceptible to luminal H+ when compared with the adult. In the present study we investigate the role of endogenous prostaglandins (PG) in the ontogeny of gastric permeability responses to H+. Responses to luminal instillation of 250 mN HCl were measured in rats at 10, 15, 20, and 25 days after birth. Mucosal responses were measured in terms of loss of H+ and appearance of Na+, K+, and protein in the luminal instillate. Indomethacin (IM; 8 mg/kg sc) administration to rat pups reduced mucosal levels of prostaglandin E2 (PGE2) and 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha). In response to intraluminal HCl, the reduction of mucosal PG did not significantly affect transmucosal fluxes of ions and protein when compared with control pups. IM was also given to lactating dams on days just prior to the pups being 10, 15, 20, and 25 days old. IM treatment significantly reduced the content of PGE2 and 6-keto-PGF1 alpha in maternal milk. Permeability responses in pups from IM-treated dams were increased over pups from control dams. This effect was not observed in 25-day-old rats. Treatment of pups from IM-injected dams with PGE2 but not PGI2 partially restored the permeability responses to luminal H+ to levels observed in pups from control dams.(ABSTRACT TRUNCATED AT 250 WORDS)

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