e n v i r o n m e n t a l t o x i c o l o g y a n d p h a r m a c o l o g y 3 5 ( 2 0 1 3 ) 161–170
Available online at www.sciencedirect.com
jo u r n al hom ep age: www.elsevier.com/locate/etap
Ontogenetic influence on rat susceptibility to lindane
seizure after pretreatment with phencyclidine
Olivera Stanojlovi´ c
a,∗
, Tatjana Nikoli´ c
b
, Dragan Hrnˇ ci´ c
a
, Nevena Radonji´ c
b
,
Aleksandra Raˇ si´ c-Markovi´ c
a
, Duˇ san Mladenovi´ c
c
, Nata ˇ sa Petronijevi´ c
b
a
Laboratory of Neurophysiology, Institute of Medical Physiology “Richard Burian”, Faculty of Medicine, University of Belgrade,
Vi ˇ segradska 26/II, 11000 Belgrade, Serbia
b
Institute of Medical and Clinical Biochemistry, Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia
c
Institute of Pathophysiology “Ljubodrag Buba Mihailovi´ c”, Faculty of Medicine, University of Belgrade, Dr Subotica 9,
11000 Belgrade, Serbia
a r t i c l e i n f o
Article history:
Received 1 August 2012
Received in revised form
23 November 2012
Accepted 2 December 2012
Available online 20 December 2012
Keywords:
Phencyclidine
Lindane
Seizures
Electroencephalography
Schizophrenia
a b s t r a c t
The aim of the study was to determine the effects of early postnatal PCP treatment on
the sensitivity of pubertal and adult rats to lindane proepileptogenic effects. Rat pups were
treated with NaCl (0.9%) or PCP (10 mg/kg) at postnatal days 2, 6, 9 and 12. One control (NaCl-
35) and one experimental (PCP-35) group have received lindane (4 mg/kg) at postnatal day
35, while others received lindane at postnatal day 65 (NaCl-65 and PCP-65). One week prior
to lindane treatment three gold-plated EEG electrodes were implanted. Pubertal rats had
significantly shorter latency time. After lindane, a prompt increase in power spectral density
seen in PCP-treated groups vs. control was evident earlier in PCP-65 rats. The theta waves
were significantly increased in PCP-35 and alpha rhythm in PCP-65 rats, when compared
with corresponding controls. Postnatal PCP treatment increases the synchronization of brain
electrical activity, thus contributing to the increased susceptibility to lindane.
© 2012 Elsevier B.V. All rights reserved.
1. Introduction
Schizophrenia is a severe neuropsychiatric illness that affects
about 1% of the population. The etiology of schizophrenia is
very complex and involves the interaction between genetic
and environmental factors. Manifestations of schizophrenia
include both positive (visual and auditory hallucinations,
Abbreviations: ANOVA, analysis of variance; CIR, coarse-grained information rate; EEG, electroencephalographic; GABA, gamma-
aminobutyric acid; i.p., intraperitoneally; LSCL-33, Limbic System Checklist; NMDA, N-methyl-d-aspartate; PCP, phencyclidine; PN,
postnatal; s.c., subcutaneously.
∗
Corresponding author at: Institute of Medical Physiology “Richard Burian”, Faculty of Medicine, University of Belgrade, Vi ˇ segradska 26/II,
11000 Belgrade, Serbia. Tel.: +381 11 3607 106; fax: +381 11 3607 106.
E-mail address: solja@afrodita.rcub.bg.ac.rs (O. Stanojlovi ´ c).
paranoia, delusions) and negative symptoms (social with-
drawal) as well as cognitive dysfunction (Lewis and Lieberman,
2000).
Epilepsy is a chronic brain disorder characterized by recur-
rence of epileptic seizures (Blume, 2001), that in more than 30%
of patients remains uncontrolled, despite extensive search
for adequate therapy. The association between epilepsy and
schizophrenia-like psychosis has attracted the attention of
1382-6689/$ – see front matter © 2012 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.etap.2012.12.006