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At least 19 recordsLinked to original sources
PubMed2001

Altered activities of rat brain metabolic enzymes caused by pentylenetetrazol kindling and pentylenetetrazol--induced seizures.

The aim of our study was to investigate amino acid and energy metabolism of pentylenetetrazol (PTZ)-kindled animals. Glutamate dehydrogenase, aspartate-aminotransferase (AST), alanine-aminotransferase, gamma-glutamyltransferase, alkaline phosphatase (ALP), lactate dehydrogenase (LDH) and creatine kinase (CK) were determined in the frontal cortex, cerebellum, hippocampus and pons-medulla regions of Hannover-Wistar rats. The rats were randomly divided into four experimental groups: (a) control; (b) rats which received a single PTZ injection in a subconvulsive dose of 40 mg/kg i.p.; (c) rats which received a single PTZ injection in a convulsive dose of 50 mg/kg i.p.; and (d) PTZ-kindled rats. Kindling increased ALP activity throughout the brain, elevated AST as well as LDH activity in the frontal cortex and hippocampus and decreased CK activity in the frontal cortex and cerebellum. Acute seizures of the same intensity did not induce these alterations. The observed effects therefore are obviously linked to the kindling phenomenon and not to seizure activity. Changes appeared mainly in the frontal cortex and hippocampus, i.e. brain areas believed to be directly involved in kindling.

Animals↗
PubMed1993

The kindling model of alcohol dependence: similar persistent reduction in seizure threshold to pentylenetetrazol in animals receiving chronic ethanol or chronic pentylenetetrazol.

Rats on a chronic intermittent ethanol (CIE) regimen showed a persistent reduction in seizure threshold to the convulsant drug pentylenetetrazol (PTZ). CIE rats were given ethanol by intubation on an alternate day schedule and tested at selected intervals for seizure threshold with PTZ. A significant reduction in seizure threshold, a sign of withdrawal, was observed 20 hr after the first dose. The severity of withdrawal intensified on repetition of the ethanol administration and depression-hyperexcitability cycle, with the seizure threshold reaching a maximum decrease after 12 doses and remaining reduced up to 60 doses. The reduction in seizure threshold persisted for at least 40 days of no alcohol following the 60th dose. The long-lasting decrease in seizure threshold following CIE treatment resembled the "kindling" phenomenon produced by chronic administration of PTZ (25 mg/kg, 3 times/week). The CIE rats developed, in addition, a tolerance to the anticonvulsant action of ethanol, which occurred well after the decrease in PTZ seizure threshold, and a tolerance to the hypothermic effect of ethanol, which developed rapidly. PTZ kindled rats that had never been exposed to ethanol also exhibited tolerance to the hypothermic effect of ethanol. We propose that kindling contributes to the mechanism of the development of dependence on central nervous system depressants like benzodiazepines, barbiturates, and alcohol, drugs that act on the gamma-aminobutyric acid-A receptor chloride ion channel complex. Repeated episodes of depression and withdrawal hyperexcitability are postulated to produce kindling during the repeated withdrawal episodes.(ABSTRACT TRUNCATED AT 250 WORDS)

Alcohol Withdrawal Delirium↗
PubMed1980

Relationship between pentylenetetrazol-induced seizures and brain pentylenetetrazol levels in mice.

Pentylenetetrazol (PTZ) is often used in experimental models of epilepsy. The relationship of the PTZ-induced seizure sequence of myoclonus, clonus and hindlimb extension (TE) to brain PTZ levels has not been reported. This study examined this relationship and determined how different routes of PTZ administration affected brain PTZ uptake and seizure development. The critical brain PTZ level for onset of clonus ranged from 20 to 50 microg/g. Brain PTZ uptake was rapid after I.P. injection of PTZ convulsant dose (CD55) for clonus/and clonus onset occured at 4.0+/- 1.6 min. uptake was slower after S.C. administration; clonus onset occurred at 9.9 +/- 3.7 min. at a CD for TE (CD40), clonus onset occured at 5.1 +/- 3.0 and 2.4 +/- 2.4 min for S.C. and I.P. routes of administration, respectively. TE onset did not appear to depend solely on brain PTZ levels were falling . Factors that could modulate the appearance of TE are discussed.

Animals↗
PubMed1987

Modulation of the discriminative stimulus produced by pentylenetetrazol by centrally administered drugs.

Pentylenetetrazol is anxiogenic in humans and produces an interoceptive discriminative stimulus in rats which is mimicked by anxiogenic drugs and other treatments and antagonized by anxiolytic drugs. It was proposed that the discriminative stimulus of pentylenetetrazol originates centrally. This hypothesis was tested by injecting small amounts of anxiogenic or anxiolytic drugs into the brain and comparing their ability to mimic or block, respectively, the response to pentylenetetrazol, observed after systemic injection. Food-restricted rats were trained in a two-lever operant task to discriminate the interoceptive discriminative stimulus produced by pentylenetetrazol. Intraperitoneal or intracerebroventricular injection of Ro 5-3663 was substituted in a dose-dependent manner for the stimulus produced by systemically administered pentylenetetrazol. Diazepam injected systemically, blocked the pentylenetetrazol-like stimulus associated with Ro 5-3663 administered systemically or centrally. Midazolam injected intracerebroventricularly and in a dose-dependent manner, antagonized the discriminative stimulus produced by systemic injection of pentylenetetrazol. When injected into the amygdala, midazolam also antagonized in a dose-dependent manner the pentylenetetrazol-induced stimulus. Thus, these data suggest that there are sites in the CNS for both the initiation of a pentylenetetrazol-like stimulus by Ro 5-3663 and the antagonism of the stimulus produced by pentylenetetrazol by midazolam.

Amygdala↗
PubMed2000

Effects of compounds acting on GABA(B) receptors in the pentylenetetrazole kindling model of epilepsy in mice.

The involvement of GABA(B) receptors in the behavioural and epileptic electrocortical discharges occurring in chemical kindling induced by repeated treatments with a subconvulsant dose of pentylenetetrazole (25 mg/kg i.p.) has been investigated in CD1 mice. Behavioural and electrocorticographic epileptic seizures following kindling induced by pentylenetetrazole (25 mg/kg i.p.) were attenuated or completely antagonized in a dose-dependent manner by the GABA(B) receptor agonist R-baclofen (2 and 6 mg/kg) whilst the GABA(B) receptor antagonist 3-amino-propyl-diethoxy-methyl-phosphinic acid (CGP 35348, 25, 50 or 100 mg/kg) and 3-[1-(S)-(3, 4-dichloro-phenyl-ethyl]amino-2-(S)-hydroxy-propyl-benzyl-phosphinic acid (CGP 55845A, 10 or 20 mg/kg) produced a more rapid development of kindling and an increase in behavioural and electrocorticographic epileptic changes. In addition, all GABA(B) receptor antagonists were able to induce an increase in Fos and Jun protein expression in pentylenetetrazole (25 mg/kg i.p.) treated mice whilst the GABA(B) receptor agonist R-baclofen (2 or 6 mg/kg) attenuated the expression of Fos and Jun protein, at cortical and limbic structures. In order to study the persistence of changes induced by pentylenetetrazole kindling, different groups of mice were rechallenged with a kindling stimulus 15 or 30 days after withdrawal from the last injection of vehicle+pentylenetetrazole, R-baclofen+pentylenetetrazole or GABA(B) receptor antagonists+pentylenetetrazole. The groups receiving GABA(B) receptor antagonists+pentylenetetrazole showed a higher incidence of seizures following the kindling stimulus than mice receiving vehicle+pentylenetetrazole whilst animals treated with R-baclofen were protected from the kindling stimulus. The different effects observed following repeated treatment with the GABA(B) receptor agonist and antagonist used revealed that GABA(B) receptors are able to affect the development of the epileptic kindling state induced by pentylenetetrazole.

Animals↗
PubMed1983

Vasopressin and oxytocin content in cerebrospinal fluid and in various brain areas after administration of histamine and pentylenetetrazol.

The content of vasopressin (AVP) and oxytocin (OXT) in the septum, hippocampus, hypothalamus and cortex was determined at 5 min and 24 hr after peripheral (intraperitoneal) administration of histamine (20.0 mg/kg) and pentylenetetrazol (45.0 mg/kg) and in the cerebrospinal fluid at 24 hr after pentylenetetrazol treatment. At 5 min after administration of histamine the AVP content in the septum was increased whereas the OXT level in the various areas was not changed. At 24 hr, neurohypophyseal peptide contents were unaffected in the brain regions analyzed. Pentylenetetrazol did not alter AVP content at 5 min after its administration, however, the OXT level in the septum and the cortex was diminished. At 24 hr after administration of pentylenetetrazol a decreased AVP content in the hippocampus and in the cortex was observed. In contrast, OXT content in the cortex was increased at this time. AVP and OXT levels in CSF were not changed at 24 hr following pentylenetetrazol treatment. The present results suggest that the levels of neurohypophyseal hormones can be differentially altered in particular brain regions at short- (5 min) and long- (24 hr) term intervals after treatment with histamine or pentylenetetrazol. Long-term changes in AVP and OXT levels after pentylenetetrazol may be implicated in the amnesic properties of this convulsive drug. Furthermore, the present findings point to a possible relationship with previously reported pentylenetetrazol-induced changes in peptide levels in the CSF.

Animals↗
PubMed1992

Differential effects of various xanthines on pentylenetetrazole-induced seizures in rats: an EEG and behavioural study.

The present study deals with the EEG (electroencephalogram) and behavioural effects of a subconvulsant dose (30 mg/kg i.p.) of pentylenetetrazole in freely moving rats pretreated (100 mg/kg p.o., 1 h before pentylenetetrazole) with two classic (theophylline and caffeine) and two new (enprofylline and isbufylline) xanthines. In rats treated with vehicle, pentylenetetrazole caused a slight desynchronization of the EEG, characterized by periods of 'wave discharges', and 'spike-and-wave discharge complexes'. In rats pretreated with xanthines (theophylline or caffeine) pentylenetetrazole produced a dramatic increase in ictal seizures with the appearance of continuous spikes; concomitantly animals experienced myoclonic jerks (100%) and in some cases (ca. 20%) the animals died. In contrast, in enprofylline-pretreated rats, pentylenetetrazole induced only brief periods of wave discharges and spike-and-wave discharge complexes whose duration was significantly reduced compared to that of controls, although these discharges were associated with mild epileptic behaviour. When isbufylline-pretreated rats were challenged with pentylenetetrazole, the EEG was characterized by a short run of wave discharges (whose duration was shorter than that of other groups). No enprofylline- or isbufylline-treated rats developed seizures or died. In conclusion, only xanthines with strong adenosine A1 receptor antagonism (theophylline and caffeine) markedly enhance the EEG and behavioural effects of a subconvulsive dose of pentylenetetrazole. The present experimental approach could be used to evaluate the pro-convulsive potential of new xanthine derivatives.

1-Methyl-3-isobutylxanthine↗
PubMed1983

On the site of pentylenetetrazol-induced enhancement of auditory responses of the reticular formation: localized cooling and electrical stimulation studies.

Pentylenetetrazol (PTZ), administered systemically, enhanced the auditory responses of neurons of the mesencephalic reticular formation (MRF). Responses evoked in the mesencephalic reticular formation by electrical stimuli in several primary auditory nuclei (cochlear nucleus, superior olivary complex and lateral lemniscus, but not inferior colliculus) were also enhanced by pentylenetetrazol in the majority of cases. Bilateral cryoprobe cooling in the lateral lemniscal tract substantially reduced the auditory-evoked field potentials (EPs) in the mesencephalic reticular formation before and after administration of pentylenetetrazol. Cooling in the inferior colliculus (IC) produced a small reduction in auditory-evoked field potentials in the mesencephalic reticular formation before drug but a more substantial degree of reduction after administration of pentylenetetrazol. A relatively small degree of pentylenetetrazol-induced enhancement of the response was seen in neurons of the inferior colliculus (158% of control) as compared to that of neurons in the mesencephalic reticular formation (410%). These findings would be consistent with the reported ability of pentylenetetrazol to block presynaptic inhibition if the input from the inferior colliculus to the mesencephalic reticular formation has inhibitory as well as excitatory components. These data along with the present authors' recent finding of enhancement of response with microapplication of convulsants strongly suggest that enhancement of responses of neurons of the mesencephalic reticular formation, induced by systemically administered convulsants such as pentylenetetrazol is exerted, to a large extent, by direct actions on synaptic elements of the reticular formation.

Animals↗
PubMed1989

Pentylenetetrazol kindling in mice.

Kindling with pentylenetetrazol to produce minimal and maximal convulsions was investigated in CF-1 mice. Like electrical kindling, the kindling effect was directly proportional to the dose or the intensity of the kindling stimulus. Similarly, the kindling effect was persistent, as was emphasized by the ability to kindle with an interdose interval of 3 days and by the convulsions produced by a challenge with pentylenetetrazol 30 days after withdrawal from the kindling treatment. The changes in excitability, associated with the kindling state, appeared to be relatively selective for pentylenetetrazol, because no changes in thresholds to either electroshock or administration of picrotoxin or N-methyl-DL-aspartate correlated temporally with the persistence of kindling. The influence of two anticonvulsant drugs, ethosuximide and cannabidiol, on kindling was also investigated. Both drugs blocked the development of kindling to pentylenetetrazol-induced minimal convulsions. Of these drugs, only ethosuximide raised the minimal convulsive threshold to pentylenetetrazol. Against pentylenetetrazol-induced kindling to maximal convulsions, only cannabidiol blocked kindling and only cannabidiol raised the maximal seizure threshold for pentylenetetrazol. Although the drugs modified the kindling effect, the mechanism of the interaction is not clear.

Animals↗
PubMed1993

Regulation of brain-derived neurotrophic factor messenger RNA and protein at the cellular level in pentylenetetrazol-induced epileptic seizures.

We have examined the effects of pentylenetetrazol-induced epileptic seizures on brain-derived neurotrophic factor messenger RNA and protein and on the messenger RNA of its receptor in the rat. Pentylenetrazol, which acts at the picrotoxin recognition site of the GABAA receptor, was injected intraperitoneally and induced seizures by decreasing the inhibitory GABAergic activity. The effects of a single acute convulsive dose (50 mg/kg) of pentylenetetrazol were analysed at different time points by in situ hybridization or immunohistochemistry. Kindling was induced by daily subconvulsive injections (30 mg/kg) of pentylenetetrazol. At different time points during the kindling process, the messenger RNAs of brain-derived neurotrophic factor and trkB and the protein levels of brain-derived neurotrophic factor were analysed. We showed that brain-derived neurotrophic factor messenger RNA dramatically increased in neurons of the granule cell layer, piriform cortex and amygdala 3 h but not 6 h after an acute high dose of pentylenetetrazol, while brain-derived neurotrophic factor-like immunoreactivity was decreased in the granule cell layer and neurons of the hilus. The trkB messenger RNA was similarly increased 3 h and 6 h after the injection and returned to control levels after 24 h. The first change during the kindling development was seen after the first severe seizure: brain-derived neurotrophic factor messenger RNA was markedly increased in the piriform cortex and amygdala but not in the hippocampus. In fully kindled rats, which had several severe seizures, brain-derived neurotrophic factor messenger RNA and trkB messenger RNA were unaffected 3 h and 24 h after the last pentylenetetrazol injection. However, brain-derived neurotrophic factor-like immunoreactivity was markedly increased in the hippocampal formation 3 h, 24 h and three days after the last pentylenetetrazol injection, and still increased after 10 days. These results suggest that brain-derived neurotrophic factor may be involved in protection mechanisms after damage during seizures and in sprouting responses. The piriform cortex/amygdala seems to be an area of origin for the kindling development.

Amino Acid Sequence↗
PubMed1995

Long-term metabolic effects of pentylenetetrazol-induced status epilepticus in the immature rat.

The present study was devoted to the long-term effects of seizures induced by pentylenetetrazol in immature rats on cerebral metabolic rates in young adult animals. Seizures were induced by repetitive intraperitoneal injections of subconvulsive doses of pentylenetetrazol either in 10- (P10) or in 21- (P21) day-old rats. The long-term metabolic effects of the seizures were studied at P60 in 54 cerebral structures by means of the [14C]deoxyglucose method. At P60, metabolic activity was decreased in 10 brain regions of rats exposed to pentylenetetrazol at P10 and in 29 structures in rats exposed to seizures at P21. Among the structures whose metabolic activity was reduced at P60 by seizures occurring either at P10 or at P21 were mainly sensory, cortical and hippocampal regions plus mammillary body, i.e. all the structures metabolically characterized as most vulnerable to pentylenetetrazol-induced status epilepticus in our previous study [Pereira de Vasconcelos A. et al. (1992) Devl Brain Res. 69, 243-259]. In the animals exposed to seizures at P21, metabolic activity was also reduced at P60 in additional sensory and cortical regions, as well as in limbic, thalamic and hypothalamic nuclei, also considered as highly sensitive to short-term pentylenetetrazol-induced seizures [Pereira de Vasconcelos A. et. al. (1992)]. Rates of glucose utilization were also reduced in a few additional areas such as the monoaminergic cell groupings. In conclusion, there are some parallels between the structures metabolically most sensitive during pentylenetetrazol-induced status epilepticus in immature rats and the long-term regional metabolic decreases recorded at P60. Our data also confirm the well-known higher sensitivity to seizures during the third postnatal week in rodents.

Aging↗
PubMed2006

Long-term L-NAME treatment potentiates the blood-brain barrier disruption during pentylenetetrazole-induced seizures in rats.

We investigated whether the severity of blood-brain barrier disruption caused by pentylenetetrazole-induced seizures is modified by long-term nitric oxide synthase inhibition in rats. Rats were given N-omega-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor, in drinking water for 4 weeks, and then treated with pentylenetetrazole to induce seizures. Damage to the blood-brain barrier was investigated using Evans blue dye extravasation. Serum nitric oxide concentration was decreased in L-NAME-treated rats (P<0.01). L-NAME and/or pentylenetetrazole treatments elevated systolic blood pressure of animals (P<0.01). L-NAME caused an increase in the mortality rate after pentylenetetrazole injection leading to the death of animals at about 15 min after the onset of the seizure. Pentylenetetrazole-induced seizures in rats treated with L-NAME caused a significant increase in Evans blue dye extravasation into cerebral cortex, diencephalon and cerebellum, as compared with seizures evoked by pentylenetetrazole injection to L-NAME-untreated rats (P<0.01). Data presented here suggest that the degree of blood-brain barrier disruption induced by seizures is more pronounced in long-term nitric oxide deficiency.

Animals↗
PubMed1997

Excitatory amino acid antagonists and pentylenetetrazol-induced seizures during ontogenesis. IV. Effects of CGP 39551.

We determined anticonvulsant effects of CGP 39551 [(E)-2-amino-4-methyl-5-phosphono-3-pentenoic acid 1-ethylester] against pentylenetetrazol-induced seizures in developing, 7-90 day old, rats. The rats received CGP 39551 in doses of 10, 20 or 40 mg/kg IP 30 min prior to the pentylenetetrazol administration (100 mg/kg s.c.). In addition, the 20 mg/kg dose of CGP 39551 was injected 120 min prior to pentylenetetrazol. In adult rats, all doses of CGP 39551 blocked generalized tonic-clonic pentylenetetrazol-induced seizures. In younger rats, higher doses of CGP 39551 and/or a longer delay between the CGP 39551 pretreatment and pentylenetetrazol administration was necessary for similar anticonvulsant effects against tonic-clonic seizures. In contrast, there was no effect of CGP on pentylenetetrazol-induced clonic seizures. The results indicate that CGP 39551 has anticonvulsant features similar to other competitive NMDA receptor antagonists. High doses of CGP 39551 and long pretreatment latency which are necessary in young rats for anticonvulsant effects may reflect the overexpression of NMDA transmission during the second and third postnatal week of the rat. Alternatively in adult rats, we can speculate an anticonvulsant role of a CGP 39551 metabolite or maturation of brain uptake mechanism for CGP 39551.

2-Amino-5-phosphonovalerate↗
PubMed1999

Effects of pentylenetetrazole-induced kindling on thyrotropin-releasing hormone biosynthesis and receptors in rat brain.

It has been postulated that changes in thyrotropin-releasing hormone biosynthesis may be involved in the mechanism of kindling--an animal model of epileptogenesis. To test this hypothesis, a time-course study was carried out to investigate the effects of pentylenetetrazole kindling (40 mg/kg i.p., daily for eight days) on the expression of gene coding for preprothyrotropin-releasing hormone, the thyrotropin-releasing hormone tissue level and thyrotropin-releasing hormone receptor parameters in rat brain. As shown by an in situ hybridization study, a single, convulsant dose of pentylenetetrazole (70 mg/kg i.p.) increased the preprothyrotropin-releasing hormone messenger RNA level in the dentate gyrus of the hippocampal formation and piriform cortex after 3 h and, to a greater extent, after 24 h. Those changes were accompanied with increases in the thyrotropin-releasing hormone level in the striatum, hippocampus, amygdala and piriform cortex. Seven days after single pentylenetetrazole administration, the thyrotropin-releasing hormone level was still significantly elevated in the piriform cortex and striatum. Acute pentylenetetrazole decreased the density (Bmax) of thyrotropin-releasing hormone receptors in the striatum after 3 and 24 h, and increased that density in the piriform cortex and amygdala after 24 h and seven days, respectively. The thyrotropin-releasing hormone receptor affinity (Kd) was decreased in the striatum and increased in the amygdala after only 3 h. Kindled rats showed a moderate increase in the preprothyrotropin-releasing hormone messenger RNA content in the dentate gyrus of the hippocampal formation and piriform cortex after 3 and 24 h; however, a significant decrease in those parameters was found after 14 days. After 3 and 24 h, pentylenetetrazole kindling also elevated the thyrotropin-releasing hormone content in the hippocampus, piriform cortex, and striatum (in the latter structure after 24 h only), whereas in the septum the thyrotropin-releasing hormone level was decreased. After seven days, the thyrotropin-releasing hormone level was still elevated in the hippocampus and piriform cortex of kindled rats, but after 14 days it was significantly lowered in the hippocampus. The kindled rats also showed a significant decrease in the density (Bmax) of thyrotropin-releasing hormone receptors in the striatum (after 24 h, seven and 14 days), and an increase in the piriform cortex (after seven days). The thyrotropin-releasing hormone receptor affinity (Kd) value was increased in the hippocampus after seven and 14 days, and in the piriform cortex after seven days. These results indicate that pentylenetetrazole kindling induces long-lasting alterations in the thyrotropin-releasing hormone biosynthesis and thyrotropin-releasing hormone receptor affinity in discrete regions of rat brain. These region-specific changes, in particular down-regulation of the thyrotropin-releasing hormone biosynthesis in the hippocampus, may be involved in chronic neuronal hyperexcitability associated with kindling.

Amygdala↗
PubMed2000

Progesterone and testosterone modulate the convulsant actions of pentylenetetrazol and strychnine in mice.

The influence of progesterone and testosterone on the incidence of seizures after administration of intraperitoneal pentylenetetrazol and subcutaneous strychnine was evaluated in mice. Pentylenetetrazol and strychnine were administered in doses that induced seizures in 40-50% of control mice in dioestrus (48 and 0.9 mg/kg, respectively). The percentage of seizures induced by pentylenetetrazol and strychnine was significantly lower in female mice in prooestrus/oestrus, when progesterone levels are high, than in dioestrus, when progesterone levels are low. Pretreatment of pentylenetetrazol-challenged mice with progesterone (250 microg/kg) increased the incidence of seizures in prooestrus/oestrus, without affecting seizures in dioestrus. The same pretreatment in strychnine-challenged mice also increased the incidence of seizures in prooestrus-dioestrus, but significantly reduced the incidence of seizures in dioestrus. In addition, progesterone pretreatment significantly increased the percentage of deaths induced by strychnine in prooestrus-oestrus, reducing deaths in dioestrus. Orchidectomized male mice had a significantly higher incidence of seizures after administration of pentylenetetrazol and strychnine than control mice. Administration of 11 daily doses of 250 microg/kg of testosterone to castrated mice significantly reduced the incidence of seizures induced by pentylenetetrazol. These results confirm the modulatory influence of reproductive steroids on the excitability of the central nervous system and the possible clinical importance of progesterone and testosterone in the management of partial epilepsy.

Animals↗
PubMed1994

Pentylenetetrazol elicits epileptiform activity in the dentate gyrus of the urethane anesthetized rat by activation of the entorhinal cortex.

Pentylenetetrazol is a chemical convulsant, often used to generate experimental seizures, that is thought to act as a GABA antagonist. In the urethane anesthetized rat, pentylenetetrazol produces a characteristic epileptiform discharge in the dentate gyrus. The hypothesis that this discharge is generated by activity in the entorhinal cortex was examined in this study. Recording electrodes were placed in the dentate gyrus bilaterally and neuronal activity was recorded after administration of pentylenetetrazol. A laminar analysis of the convulsant-induced activity was compared to responses evoked by angular bundle stimulation (n = 6). Both convulsant-induced and evoked activity were negative-going in the molecular layer of the dentate gyrus. In other animals tetrodotoxin (TTX) was injected into the right entorhinal cortex before the onset of epileptiform activity (n = 5). The TTX prevented epileptiform activity in the right dentate gyrus. Injection of TTX after the onset of epileptiform activity caused the epileptiform activity to cease on the side of injection (n = 5). These experiments support the hypothesis that pentylenetetrazol specifically activates the entorhinal cortex to produce the epileptiform activity recorded in the dentate gyrus. This selective activation suggests that the mechanism of action of pentylenetetrazol, as a convulsant, is not simply as an antagonist of GABA receptors.

Anesthesia↗
PubMed1981

Effect of acute and chronic pentylenetetrazol treatment on benzodiazepine and cholinergic receptor binding in rat brain.

The binding of [3H] diazepam and [3H] flunitrazepam in rat cerebral cortex was not altered by either acute or chronic administration of pentylenetetrazol except in rats made to convulse 30 min before sacrifice. Rats treated for up to 6 months with doses of pentylenetetrazol which are below seizure threshold in naive rats, became increasingly sensitive to the CNS stimulant effect of pentylenetetrazol as demonstrated by the development of myoclonus and convulsions during treatment periods. These effects were not correlated with any changes in benzodiazepine binding in cerebral cortex or cerebellum and [3H] quinuclidinyl benzilate binding in cerebral cortex. Acute convulsant doses of pentylenetetrazol increased benzodiazepine binding in cerebral cortex, but only in those rats which actively convulsed. Benzodiazepine and cholinergic receptors of the cortex, and benzodiazepine receptors of the cerebellum, therefore, do not appear to change with either the acute or chronic subconvulsive administration of pentylenetetrazol.

Animals↗