Spatial learning deﬁcits and emotional impairments
in pentylenetetrazole-kindled rats
, Mathew Ericson
, Darren Story
, Verne D. Hulce
, Gary L. Dunbar
Brain Research and Integrative Neuroscience Center, Department of Psychology, Central Michigan University, Mt. Pleasant, MI 48859, USA
Field Neurosciences Institute, Saginaw, MI 48604, USA
Received 8 July 2005; revised 18 August 2005; accepted 20 August 2005
Available online 24 October 2005
Pentylenetetrazole (PTZ) is a chemical kindling agent used to examine the eﬃcacy of potential anticonvulsants in rats. However, the
extent to which PTZ mimics postseizure symptoms of epilepsy has not been thoroughly examined. This study assessed whether PTZ-in-
duced seizures produce cognitive and emotional deﬁcits that mimic those observed in many epileptic patients. Rats were given 30 mg/kg
PTZ or vehicle (intraperitoneally) every other day for 28 days. Those rats exhibiting consistent seizure activity were tested for learning
ability and emotional reactivity, beginning 1 week following a single challenge dose of PTZ. Rats given PTZ made more reference mem-
ory errors in a radial arm water maze task, and exhibited emotional abnormalities in the forced swim test, the systematic handling test,
and the open-ﬁeld exploratory maze. Histological analysis revealed neuronal loss in the CA1 area and increased mossy ﬁber sprouting in
the dentate gyrus, similar to what is observed in human epilepsy. These results indicate that PTZ kindling provides a useful model of
postseizure dysfunction, which can serve as a screen for potential treatments for those cognitive, emotional, and neuropathological def-
icits that resemble those symptoms observed in human epilepsy.
Ó 2005 Elsevier Inc. All rights reserved.
Keywords: Pentylenetetrazole; Kindling; Spatial learning; Radial arm water maze; Behavior; Epilepsy; Fear; Depression; Aggression; Open ﬁeld
Epilepsy is characterized by recurrent seizures due to
excessive discharge of cerebral neurons. These recurrent
seizures can produce cognitive deﬁcits, emotional impair-
ments, and psychosocial problems [1–4]. Seizure-induced
cognitive impairments have been reported for both chil-
dren and adults [1,5–10]. Furthermore, speciﬁc deﬁcits in
spatial reference memory and short-term memory have
also been reported in patients with temporal lobe epilepsy
[11,12]. Using the nine-box maze test, which is similar to
the radial-arm-maze task, Abrahams et al.  found both
working and reference memory deﬁcits in patients with
In addition to problems with memory and other cogni-
tive processes, many patients with epilepsy have also been
diagnosed with aﬀective and personality disorders [3,13].
Of these disorders, depression and anxiety are most com-
mon, with more than 50% of patients with epilepsy being
diagnosed with depression , many of these being
comorbid with anxiety . Depression has been described
during the prodromal, ictal, postictal, and interictal peri-
ods, with interictal depression occurring most frequently
. As with depression, patients with epilepsy have also
been reported to have a high incidence of aggression, espe-
cially during the postictal period [15,16]. Aggression can
also occur in the context of postictal psychosis, which,
when present, usually starts a few days after the occurrence
of seizures .
Kindling models of epilepsy have been developed to
test potential antiepileptic drugs and to deﬁne more pre-
cisely the possible etiology of the disorder. Kindling can
1525-5050/$ - see front matter Ó 2005 Elsevier Inc. All rights reserved.
Corresponding author. Fax: +1 989 774 2553.
E-mail address: firstname.lastname@example.org (G.L. Dunbar).
Epilepsy & Behavior 7 (2005) 629–638