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Models _ Models of Generalized Seizures in Freely Moving Animals
Freely Moving Animals; Seizure Models in Acute and
Organotypic Slices; Seizure Predisposition and Expression in the Genetic Epilepsies as Exemplified by the
Genetically Epilepsy-Prone Rats; Temporal Lobel Epilepsy in Humans: Searching for Answers through the
Pilocarpine Model; The Tetanus Toxin Model of Temporal
Lobe Epilepsy.
Further Reading
Avanzini G, Treiman DM, and Engel J, Jr. (2008) Animal models of
acquired epilepsies and status epilepticus. In: Engel J, Jr and Pedley
TA (eds.) Epilepsy: A Comprehensive Textbook, 2nd edn.,
Philadelphia: Lippincott Williams & Wilkins, pp. 415–444.
Baraban SC (2007) Emerging epilepsy models: Insights from mice, flies,
worms and fish. Current Opinion in Neurology 20: 164–168.
Engel J Jr. (1992) Experimental animal models of epilepsy: Classification
and relevance to human epileptic phenomena. Epilepsy Research
(Supplement 8 ): 9–20.
Engel J Jr. (1998) Research on the human brain in an epilepsy surgery
setting. Epilepsy Research 32: 1–11.
Engel J Jr. (2006) Report of the ILAE Classification Core Group.
Epilepsia 47: 1558–1568.
Jefferys JGR (2008) Epilepsy in vitro: Electrophysiology and computer
modeling. In: Engel J, Jr and Pedley TA (eds.) Epilepsy:
A Comprehensive Textbook, 2nd edn., Philadelphia: Lippincott
Williams & Wilkins, pp. 457–468.
Noebels JL (2008) Genetic models of epilepsy. In: Engel J Jr and Pedley
TA (eds.) Epilepsy: A Comprehensive Textbook, 2nd edn.,
Philadelphia: Lippincott Williams &Wilkins, pp. 445–455.
Pitkänen A, Schwartzkroin PA, and Moshé SL (2006) Models of Seizures
and Epilepsy, p. 687. San Diego: Elsevier.
Purpura DP, Penry JK, Tower DB, Woodbury DM, and Walter RD (eds.)
(1972) Experimental models of epilepsy – A manual for the laboratory
worker. New York: Raven Press.
Schwartzkroin PA (1993) Epilepsy. Models, Mechanisms and Concepts.
Cambridge: Cambridge University Press.
Swann JW, Baram TZ, Jensen FE, and Moshé SL (2008) Seizure
mechanisms and vulnerability in the developing brain. In: Engel J, Jr
and Pedley TA (eds.) Epilepsy: A Comprehensive Textbook, 2nd
edn., Philadelphia: Lippincott Williams & Wilkins, pp. 469–479.
Models of Generalized Seizures in Freely Moving Animals
L Velı́šek, Albert Einstein College of Medicine, Bronx, NY, USA
ã 2009 Elsevier Ltd. All rights reserved.
Models of generalized seizures are frequently used in
the pharmaceutical industry for initial testing of novel
compounds for anticonvulsant activity. These models historically include maximal electroshock seizures and minimal pentylenetetrazol seizures. The drugs active against
tonic hindlimb extension seen in maximal electroshock
seizures were thought to prevent seizure spread; drugs
active against minimal pentylenetetrazol seizures (also
referred to below as clonic seizures) were thought to
increase seizure threshold. These two models still carry
some value for routine drug testing, for their simplicity
and high throughput.
The current choice of models of generalized seizures
is much wider, and more complex models of generalized
seizures in freely moving animals have an important use
in research. These models may yield interesting information about responsiveness of the nervous system to
convulsant drugs – i.e., about propensity of the brain to
respond with seizure activity to external stimuli. This
seizure susceptibility may be modified by many factors,
including genetic conditions, hormonal milieu, previous
seizure experience, and environmental conditions (e.g.,
stress). Models of generalized seizures can be used to
determine efficacy of antiepileptic drugs under various
conditions. Since different models utilize alterations in
different neurotransmitter systems, these studies may
help to elucidate mechanisms of antiepileptic drug
action. Finally, if action of convulsant drugs is studied
during early postnatal development, information can be
gathered about nonlinear evolution of seizure propensity of the developing brain.
Many convulsant drugs administered systemically
stimulate either the entire brain (bilateral effects) or
they activate those brainstem structures projecting bilaterally to upper brain regions. This view is based on
current EEG and imaging techniques. The resulting seizures will be perceived as stemming from the entire brain
(or at least from the EEG-accessible parts), and considered as primarily generalized. In contrast, some convulsant drugs may create a strong unilateral source (focus) of
epileptic activity as identified by current technology,
and epileptic activity will spread from this focus bilaterally. These seizures will then be considered secondarily
Primary generalized seizures – seizures that appear to arise
simultaneously over broad regions of the brain – are very
common in the human population. Examples of human
primarily generalized seizures are absence seizures,
776 Models _ Models of Generalized Seizures in Freely Moving Animals
generalized clonic seizures, and generalized tonic-clonic
seizures. Animal research and improved diagnostic techniques (especially imaging) have recently led to the view that
at least some of the seizures previously categorized as
‘primary generalized’ are actually of focal origin (e.g., in
the somatosensory cortex), but spread rapidly (i.e., are actually secondarily generalized). Without question, however,
primary generalized seizures constitute a significant proportion of the seizure types seen clinically. Models of
generalized seizures in experimental animals contribute a
great deal to understanding the mechanisms of seizure
spread and control, and also to the search for better antiepileptic therapy; indeed, two generalized seizure models
are used for routine testing of newly synthesized compounds (see earlier text). In addition, many epileptic syndromes of childhood involve primarily generalized seizures.
Examples of these syndromes are early myoclonic encephalopathies (newborns), infantile spasms (age: 3–12 months),
and Lennox-Gastaut syndrome (age: 1–8 years). While current animal models of generalized seizures correspond very
well to human generalized clonic, tonic-clonic, and absence
seizures, the satisfactory models for many childhood epileptic syndromes involving generalized seizures still do not
exist. Recently, better models for infantile spasms have been
developed (see Stafstrom and Velı́šek), giving the field an
opportunity to study underlying mechanisms and more
effective therapeutic agents for this catastrophic seizure
syndrome of childhood. However, there is a pressing need
to develop models for other catastrophic seizure syndromes
(associated with progressive mental retardation and, frequently, death) in order to improve current therapy. Appropriate and accurate animal models can provide insights into
pathogenesis of these syndromes, and lay the foundation for
future mechanistic treatments.
Generalized (either primarily or secondarily) seizures can
be induced in freely moving animals by systemic injection
of chemical substances (convulsant drugs), by direct electrical stimulation of the brain, or they can develop from
genetic defects. Models based on systemic injection of
convulsant drugs require very simple equipment: a syringe
with an appropriate size needle, a convulsant drug in a
solution, an observation cage, and a stop-watch. Needle size
depends on the density of the injected solution and, of
course, on the route of administration. Subcutaneous injection (usually in the skin fold on the back of the neck)
requires a fine needle (26 gauge), while administration
of a dense solution intraperitoneally will require larger
needle, 22–24 gauge. Intravenous administration may be
more complicated. The tail vein is commonly used in rats.
However, to access this vein, the rat must be well restrained
during the entire injection procedure. While very simple,
the administration of convulsant drugs by injection produces also significant stress (restraint, pain), which may be
hard to standardize for the experimental groups. Alternatively, inhalation of the convulsant ether (flurothyl) can be
used to elicit generalized seizures. Flurothyl evaporates
easily at room temperature. Since it has convulsant features
in both experimental animals and human experimenters, an
air-tight cage must be used and the entire system should be
placed in the fume hood for additional protection. This
arrangement also requires use of a precision microinfusion
pump, which delivers flurothyl into the air-tight chamber
at a constant rate (although other approaches – e.g., bolus
delivery to the air-tight chamber – are also possible).
General electrical stimulation of the entire brain (maximal electroshock) is theoretically possible in freely moving
animals, but impractical because the stimulating current is
delivered via ear-clip electrodes that easily displace. Therefore, maximal electroshock is generally given with animals
restrained. In freely moving animals, electrical stimulation
of specific brain sites via implanted electrodes can be used
to generate an epileptic focus and secondarily generalized
seizures. Additionally, this procedure may be used to model
the process of epileptogenesis (i.e., kindling from the focus).
Furthermore, some convulsant drugs although injected systemically preferentially affect a restricted part of the brain
(because of very high receptor density). These drugs even
with systemic administration can be used to create a seizure
focus with secondarily generalization.
Pentylenetetrazol-induced seizures are elicited most
commonly by a bolus dose of subcutaneous or intraperitoneal aqueous solution of pentylenetetrazol, between
40–120 mg kg 1 in both rats and mice. Pentylenetetrazol
administration results in blockade of GABA(A) receptor
(via the TBPS site in the chloride channel). Delivery
of graded pentylenetetrazol doses intravenously is also
possible; such an approach can be used to determine
seizure threshold or threshold of individual components
of pentylenetetrazol-induced seizures.
Bicuculline and Picrotoxin
Both drugs are GABA(A) receptor antagonists. Bicuculline
competes with GABA on its binding site, while picrotoxin
occupies its own binding site in the associated chloride
channel. Bicuculline cannot be easily dissolved in water or
saline. Those bicuculline salts, which can be dissolved in
water, do not cross blood-brain barrier, and therefore cannot
be used for systemic administration in adult animals. Therefore, bicuculline is usually dissolved in 0.1 N HCl and pH is
titrated back with 0.1 N NaOH. The final pH will be acidic,
and thus painful if injected in the area with abundant nerve
endings. Hence, bicuculline solution should be
Models _ Models of Generalized Seizures in Freely Moving Animals
preferentially administered intravenously (around 2 mg
kg 1), as a second choice intraperitoneally (6–8 mg kg 1),
and only exceptionally subcutaneously. In adult animals,
intraperitoneal administration is limited by the ‘first-pass’
effect, during which the mature liver enzymatic system
metabolizes a large portion of the injected drug, resulting
in substantially higher dosage required for the same convulsant effects than during intravenous administration. Picrotoxin, on the other hand, can be dissolved in saline. Doses
between 3–6 mg kg 1 are usually injected intraperitoneally.
Flurothyl is a liquid ether, usually delivered by a precision
microinfusion pump into an air-tight chamber. The rate of
delivery depends on the chamber size. We use chambers
between 9 and 14 l (volume), with a CO2 scavenger. For
these chambers, flurothyl delivery at 20–40 ml min 1 leads
to seizure occurrence in mice or rats within 8–12 min.
With continuous flurothyl delivery, the latency to onset of
seizure marks the seizure threshold. The seizures are the
result of flurothyl blockade of GABA(A) receptors, with
the addition of opening of sodium channels and activation
of the cholinergic system.
Strychnine sulfate can be dissolved in normal saline (at
1 mg ml 1) and doses for adult rats are between 2–3 mg
kg 1 subcutaneously. Seizures are elicited by blockade of
glycine-operated chloride channels, which are abundant in
the spinal cord and brain stem.
Kainic Acid (KA)
KA-induced seizures are usually induced by a systemic
injection of aqueous solution of KA (with pH adjustment,
although the final pH is still acidic), a neurotoxic analog of
glutamate with preferential effects in the limbic system.
Frequently, a bolus dose of KA is administered intraperitoneally. In rats this bolus dose is between 10–20 mg kg 1,
while mice usually require a higher dose, between
20–40 mg kg 1. An alternative approach is to infuse graded
doses of KA in the tail vein (in rats, 2.5–5 mg kg 1 every
5–20 min) until seizures occur.
N-Methyl-D-Aspartate (NMDA)
NMDA can be dissolved in saline up to 50 mg ml 1.
Systemic doses that induce seizures in adult rats range
between 150–300 mg kg 1. NMDA activates NMDA subtype of glutamate receptors. NMDA doses for eliciting
seizures in developing rats are an order of magnitude
lower than for the adult rats, at least in part because of
better blood-brain barrier permeability in immature
brain. Another reason for this higher sensitivity to
NMDA may be the transiently increased NMDA receptor
density in the immature brain, and the different subunit
composition of NMDA receptors in infancy (high content
of the NR2B subunit).
Maximal Electroshock Seizures
For maximal electroshock seizures, a device capable of
delivering currents up to 300 mA is required (high voltage!). Current is delivered via ear-clip electrodes and the
normal range is between 150–200 mA for seizure induction in rats. The rat is usually restrained during the
stimulation protocol.
Delivery of short (1–2 s) trains of alternating current (either
sinusoid or rectangular pulses), at frequencies 50–60 c s 1
(Hz), at regular intervals, which is initially subthreshold for
generalized seizure discharge and eventually leads to
evoked seizures, is called kindling. The principle of kindling consists in delivery of subthreshold stimulus for motor
seizures. With repetitions of this stimulus at appropriate
intervals (4–48 h in adult rats) the seizures develop, become
more and more severe, and also permanent. While initial
stimulations produce focal electrical discharges (focal afterdischarges must be induced by the kindling stimulus),
repeated stimulations lead to more severe stages of motor
seizures, which represent secondary generalization.
Genetic Models
There are two well developed genetic models of primarily
generalized absence seizures. One model was discovered
in Strasbourg (Genetic Absence Epilepsy Rat from
Strasbourg, GAERS) and the other in The Netherlands
(WAG/Rij rat). Both strains are viable and reproduce
well. There is also a genetically-based model of generalized
seizures precipitated by loud sound (Genetically EpilepsyProne Rat; GEPR). In addition, several models of spontaneously occurring seizures in mutant mice are available.
Drugs Affecting GABAA Receptors
Pentylenetetrazol, bicuculline, picrotoxin and flurothyl
significantly block GABAA receptor function. Therefore,
seizures induced by these drugs have many common
features: Low doses of these convulsants (or early during
the induction phase) elicit behavioral arrest and staring. In
the EEG, spindle-shaped trains of spike-and-wave are
recorded (Figure 1). Later during induction (or with
moderate doses), myoclonic whole body twitches occur,
accompanied by individual spikes on the EEG (often
778 Models _ Models of Generalized Seizures in Freely Moving Animals
Kainic Acid
500 µV
Figure 1 Initial EEG activity produced by low dose of s.c.
bicuculline in the adult rat (rhythmic bicuculline-induced activity).
Trace legend indicates areas of neocortex, in which recordings
have been performed. Spindle-shaped spike and wave activity is
marked with arrowheads in the left frontal cortex, yet can be seen
in all traces. Calibration 500 mV, time mark 1 s.
Table 1
Developmental specificity of clonic seizures induced
by GABA(A) receptor acting convulsant drugs in rats
KA induces developmentally specific seizure syndromes.
In adult rats, after automatisms consisting of rapid and
alternating head rotations (‘wet dog shakes’) or rarely of
scratching, clonic seizures of face and forelimbs occur with
preserved righting. These convulsions are sometimes
termed ‘limbic seizures,’ a term that emphasizes the focal
initiation of epileptic activity. At the time of clonic seizure
development, epileptic activity is already secondarily
generalized and the seizure pattern is similar to the pattern
described above (i.e., the clonic seizures seen in flurothyl,
pentylenetetrazol, bicuculline or picrotoxin seizure models). In adult animals, tonic-clonic seizures after KA are
rare; however, clonic seizures may last for many minutes
to hours, developing into status epilepticus (continuous
seizure activity lasting 30 min and more). Severity of
the status epilepticus episodes correlates with the degree
of resulting neuronal damage in the hippocampus. Epileptic EEG activity precedes motor seizures, and can be
recorded earlier in limbic structures than in the neocortex.
Ages indicate postnatal days in rats. Full line marks regular
occurrence of clonic seizures, if sufficient dose of the convulsant drug is used. Dotted line indicates infrequent or even
rare occurrences.
overlapping with movement artifacts). After myoclonic
twitches, clonic seizures of forelimbs and face develop.
These seizures last for several seconds to tens of seconds.
If the clonic seizure is severe enough to disturb upright
posture, the animal immediately and actively regains
balance. In the EEG, the seizure presents as a series of
spike-and-wave discharges. Finally, with larger doses
of convulsant, or after longer time intervals, tonic-clonic
seizures occur. These seizures begin with wild running,
followed by the loss of righting ability. While lying on the
cage floor, the animal displays tonic extension of limbs,
concomitant with clonus of all four limbs. On the EEG,
seizures usually start with fast polyspikes followed by
spike-and-wave complexes. All features occur throughout
development except for clonic seizures, which are developmentally specific and also dependent on the convulsant
drug (Table 1).
This drug produces myoclonic twitches and tonic-clonic
seizures with loss of righting. During the seizures, extensions of the trunk, limbs, and tail are prominent. The EEG
correlate of these strychnine-induced seizures are predominantly spikes and sharp waves.
In adult animals, NMDA induces periods of wild running
followed by generalized clonic seizures with complete loss
of righting ability. This seizure pattern is similar to the
tonic-clonic seizure pattern described above after pentylenetetrazol, flurothyl, bicuculline or picrotoxin. However, tonic seizure phase follows, rather than precedes,
the clonic phase. Usually the occurrence of the tonic
phase indicates a lethal ending for the seizure. Cortical
EEG associated with NMDA injection is very nonspecific,
consisting of periods of EEG suppression and polyspikeand-wave discharges.
Maximal Electroshock Seizures (MES)
Maximal electroshock delivered via ear-clip electrodes
immediately produces tonic-clonic convulsions with the
loss of righting. If the current is strong enough, the following sequence occurs: tonic flexion of forelimbs, tonic flexion of hindlimbs, tonic extension of forelimbs and tonic
extension of hindlimbs. Prolonged tonic hindlimb extension frequently marks the end-point of the experiment.
Stimulation of a sensitive brain structure, such as hippocampus, amygdala, entorhinal cortex, etc., delivered at low
intensity, produces an EEG afterdischarge (Figure 2). With
repeated stimulations, the duration of afterdischarges
increases and behavioral seizures develop. These seizures
have a character of clonic seizures of face and forelimbs,
with preserved righting ability, as described above for
Models _ Models of Generalized Seizures in Freely Moving Animals
Right hippo
Left hippo
500 µV
Figure 2 Afterdischarge following hippocampal stimulation in the adult rat. Trace legend indicates areas of neocortex, in which
recordings have been performed. Left and right hippo indicate recordings from the left and right hippocampus. Arrowhead points to the
end of stimulation (electrode in the left hippocampus). The afterdischarge consisting of spike-and-wave complexes follows (well seen in
the trace recorded in the right hippocampus) with cessation about 2 s after a ‘wet dog shake’ (W) occurred. Calibration 500 mV, time
mark 1 s.
convulsant drugs acting at GABAA receptors. Behavioral
seizures also evolve, and can be classified according to the
widely accepted Racine scale (Table 2). Once the stage 4
seizures occur, the seizures are considered secondarily
Genetic Models
Both GAERS and WAG/Rij rat strains develop EEG
activity consisting of periods of spike and wave rhythms,
with crescendo-decrescendo amplitude (spindle shaped)
resembling the 3 Hz spike-and-wave discharges in human
absence epilepsy. Behaviorally, these EEG episodes are
accompanied by motionless stare. Another rat model, the
GEPR, comes in two variants: GEPR-3s show moderate
clonic seizures, and GEPR-9s exhibit severe tonic-clonic
seizures with the behavioral seizure patterns very similar
to those described above for GABAA receptor acting drugs.
Future Goals
Our discussions in this article should convince the reader that in the current era of molecular and cellular neurobiology, there is still significant room for models
of generalized seizures in freely moving animals. Sometimes
it is difficult to determine what these models model, what
the underlying mechanisms might be, and what the consequences of these seizures are for the brain. However,
there are precise fits for some models – e.g., the genetic
absence models in rats provide important insights into the
mechanisms of absence seizures in humans, most recently
suggesting focal cortical origins of spike-and-wave absence
Table 2
Racine scale for kindling-induced generalized
seizures in adult rats
Behavioral expression
Mouth and facial movements
Head nodding
Clonus contralateral to the stimulus site
Symmetrical forelimb clonus with rearing
Rearing and falling (yet regaining upright position)
There is a need to investigate old models of generalized seizures, and to create new ones. There are several
reasons why new models are necessary: (1) New models
may better reflect the human condition, and thus help to
improve studies of the disease mechanisms. (2) For some
human seizure syndromes, there are no corresponding
animal models. For example, our understanding and treatment of Lennox-Gastaut syndrome would be immeasurably helped by research on a relevant animal model.
Similarly, early infantile epileptic encephalopathies have
no available models though there is an urgent need to
improve their therapy and find underlying mechanisms.
Thus, further exploitation of existing models of generalized
seizures and development of new models will play a major
role in future epilepsy research.
See also: Aging: Effects of Aging on Seizures and
Epilepsy; Models: Model Characterization in Relationship
to Human Disorders; Pharmacology of Seizure Drugs;
Seizure Predisposition and Expression in the Genetic
Epilepsies as Exemplified by the Genetically EpilepsyProne Rats; Pediatric Epilepsy: Animal Models of
Catastrophic Epilepsies of Childhood; Plasticity: LTP
and Kindling: Phenomena of Activity-Dependent Plasticity
Influencing Memory and Epilepsy.
780 Models _ Pharmacology of Seizure Drugs
Further Reading
Ben-Ari Y (1985) Limbic seizure and brain damage produced by kainic
acid: Mechanisms and relevance to human temporal lobe epilepsy.
Neuroscience 14: 375–403.
Browning RA (1984) The role of neurotransmitters in electroshock
seizure models In: Jobe PC and Laird HE II (eds.) Neurotransmitters
and Epilepsy, pp. 277–320. Clifton: Humana Press.
Browning RA, Wang C, Lanker ML, and Jobe PC (1990) Electroshockand pentylenetetrazol-induced seizures in genetically epilepsy-prone
rats (geprs): Differences in threshold and pattern. Epilepsy Research
6: 1–11.
Fisher RS (1989) Animal models of epilepsies. Brain Research Reviews
14: 245–278.
Goddard GV (1967) Development of epileptic seizures through brain
stimulation at low intensity. Nature 204: 1020–1021.
Loscher W (1997) Animal models of intractable epilepsy. Progress in
Neurobiology 53: 239–258.
Mareš P and Velı́šek L (1992) N-Methyl-D-aspartate (NMDA)-induced
seizures in developing rats. Developmental Brain Research 65:
Marescaux C, Vergnes M, and Depaulis A (1992) Genetic absence
epilepsy in rats from Strasbourg – A review. Journal of the Neural
Transmission [Suppl] 35: 37–69.
Noebels JL (2001) Modeling human epilepsies in mice. Epilepsia 42
(Suppl 5): 11–15.
Pitkanen A, Schwartzkroin PA, and Moshé SL (eds.) (2006) Models of
Seizures and Epilepsy. Amsterdam: Elsevier.
Racine RJ (1972) Modification of seizure activity by electrical stimulation:
II. Motor seizures. Electroencephalography and Clinical
Neurophysiology 32: 281–294.
Sarkisian MR (2001) Overview of the current animal models for human
seizure and epileptic disorders. Epilepsy & Behavior 2: 201–216.
Van Luitelaar G and Sitnikova E (2006) Global and focal aspects of
absence epilepsy: The contribution of genetic models. Neuroscience
& Biobehavioral Reviews 30: 983–1003.
Velı́šek L, Kubová H, Pohl M, et al. (1992) Pentylenetetrazol-induced
seizures in rats: An ontogenetic study. Naunyn-Schmiedeberg’s
Archives of Pharmacology 346: 588–591.
White HS (1997) Clinical significance of animal seizure models and
mechanism of action studies of potential antiepileptic drugs.
Epilepsia 38(Suppl.): S9–S17.
Pharmacology of Seizure Drugs
H Kubova, Academy of Sciences of the Czech Republic, Prague, Czech Republic
ã 2009 Elsevier Ltd. All rights reserved.
Introduction and Background
Epilepsy is clinically manifested in recurring, self-sustaining bursts of abnormal electrical activity (epileptic seizures) in the brain. In contrast to reactive seizures, which
occur in response to ‘environmental stimuli’ (e.g., fever,
hypoglycemia, presence of seizure-inducing agents), epileptic seizures occur at unpredictable intervals. With only
few exceptions (e.g., reflex epilepsies), seizures appear in
the absence of any clear identifiable triggers. In contrast,
isolated seizures can be induced in many different ways,
even in intact and healthy brain without any previous
experience of epileptic activity or behavior. Under experimental conditions, seizures can be induced chemically,
using seizure-inducing or convulsive drugs (chemoconvulsants). These drugs do not fall into any specific pharmacological category, and they act through many different
mechanisms. Chemoconvulsants can be used to induce
seizures in various animal species, including mammals,
invertebrates, fishes, or birds. For many experimentally
used drugs, seizure induction has also been described in
humans, for example, after overdose or accidental intoxication. Chemoconvulsants involve drugs of different origin, including plant toxins (strychnine), weapon-grade
organophosphorus substances (soman, sarin), or bacterial
toxins (tetanus toxin). Many drugs that are used clinically
for various indications can induce convulsions/seizures
when overdosed or administered in a way that leads to
nonphysiological concentrations in the brain. Some of
these drugs are used experimentally, such as aminophylline (theophylline and elhylenediamine; drug used to treat
asthma), isoniazid (antimicrobial agent used in chemotherapy of tuberculosis), lidocaine and cocaine (local anesthetics), and penicillins (antibiotics).
In experimental epileptology or pharmacology, seizures induced by chemoconvulsants represent frequently
used models, induced to study generation or generalization of epileptic activity and to search for new anticonvulsant drugs. Such models also represent powerful tools to
study effects of sex, age, genetic background, or additional
pathologies on seizure susceptibility or development. In
addition, chemoconvulsants with known mechanisms of
action can be used to study postnatal development and
functional maturation of neurotransmitter systems and
ion channels, and to investigate the role of specific systems
(e.g., neurotransmitter receptors or metabolic pathways) in
brain excitability or seizure development.
Chemoconvulsant models are inexpensive and widely
used. Their major advantage is that the procedure is simple
and convenient, and models are usually well described.
For many of these models, there are standard methods of
evaluations, with relatively standard scoring systems developed to quantify seizure severity and pattern. Thus, the
results obtained from these models are usually highly reproducible and comparable across different laboratories. There
are, however, some disadvantages that should be
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