Research Article
Anxious and Nonanxious Mice Show Similar Hippocampal
Sensory Evoked Oscillations under Urethane Anesthesia:
Difference in the Effect of Buspirone
János Horváth,
1
Balázs Barkóczi,
1
Géza Müller,
2
and Viktor Szegedi
3
1
Department of Medical Chemistry, University of Szeged, Dom Square 8, Szeged 6720, Hungary
2
Biochemistry, Biological Research Centre, Hungarian Academy of Sciences, Temesvari K¨ or´ ut 32, Szeged 6726, Hungary
3
Biological Research Centre, Hungarian Academy of Sciences, Temesvari K¨ or´ ut 32, Szeged 6726, Hungary
Correspondence should be addressed to Viktor Szegedi; szegedi.viktor@brc.mta.hu
Received 21 December 2014; Revised 17 March 2015; Accepted 17 March 2015
Academic Editor: Preston E. Garraghty
Copyright © 2015 J´ anos Horv´ ath et al. his is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Hippocampal oscillations recorded under urethane anesthesia are proposed to be modulated by anxiolytics. All classes of clinically
efective anxiolytics were reported to decrease the frequency of urethane theta; however, recent indings raise concerns about the
direct correlation of anxiolysis and the frequency of hippocampal theta. Here, we took advantage of our two inbred mouse strains
displaying extremes of anxiety (anxious (AX) and nonanxious (nAX)) to compare the properties of hippocampal activity and to
test the efect of an anxiolytic drugs. No diference was observed in the peak frequency or in the peak power between AX and nAX
strains. Buspirone (Bus) applied in 2.5 mg/kg decreased anxiety of AX but did not have any efect on nAX as was tested by elevated
plus maze and open ield. Interestingly, Bus treatment increased hippocampal oscillatory frequency in the AX but letit unaltered in
nAX mice. Saline injection did not have any efect on the oscillation. Paired-pulse facilitation was enhanced by Bus in the nAX, but
not in the AX strain. Collectively, these results do not support the hypothesis that hippocampal activity under urethane may serve
as a marker for potential anxiolytic drugs. Moreover, we could not conirm the decrease of frequency ater anxiolytic treatment.
1. Introduction
Anxiety disorders are among the most abundant afective dis-
orders, with a prevalence of 1% in the Western countries. he
neurochemistry behind this set of conditions are relatively
well described: the imbalance of the serotoninergic system
has been implicated in regulating permanently elevated
anxious mood, and a prominent class of anxiolytic drugs
used in the clinic exert their action via the serotonergic
system including serotonin reuptake inhibitors and agonists
of the serotonin 1A receptor (5-HT1AR) [1, 2]. his receptor
is most abundant in the hippocampal CA1 [3, 4], suggesting
a primary role of this brain part in regulating anxiety.
Brain oscillations are thought to govern cognitive pro-
cesses, providing temporal functional linkage between dif-
ferent brain parts and allowing the temporal separation of
functionally distinct neuronal assemblies. Among the rich
repertoire of the prominent hippocampal oscillations, theta
activity is implicated in various cognitive processes, including
locomotion, learning and memory, and alert (fear and anxi-
ety) [5, 6]. his rhythm is subject to serotonergic inluences
originating in the raphe nuclei [7–11]. Of particular interest
here, almost all classes of clinically efective anxiolytics and
compounds in the preclinical stage reduce the frequency of
hippocampal theta activity elicited by stimulation of the retic-
ular formation in freely behaving or anesthetized animals
[12]. Notable exception includes direct bilateral histamine
infusion into the lateral septum, which decreased anxiety-
like responses in two models of anxiety, the elevated plus
maze and novelty-induced suppression of feeding test in rats,
but, instead of decreasing, the same infusion signiicantly
increased hippocampal theta frequency elicited by reticular
stimulation in urethane-anesthetized rats [13]. Similar results
were reported for direct septal infusion of muscimol, which
also increased theta frequency evoked by brainstem stim-
ulation and reduced anxiety-like behaviors [14]. Moreover,
Hindawi Publishing Corporation
Neural Plasticity
Volume 2015, Article ID 186323, 9 pages
http://dx.doi.org/10.1155/2015/186323