Book of abstracts - British Neuroscience Association

19.03
Effects of early adversity on hemispheric functional connectivity
of the medial prefrontal cortex
(1, 3)Stevenson C W, (2) Halliday D M, (3) Marsden C A, (3) Mason R
(1) Leicester School of Pharmacy, De Montfort University, (2)
Department of Electronics, University of York, (3) School of
Biomedical Sciences, University of Nottingham
Early adversity increases the predisposition to develop mental illness.
Maternal separation (MS) models the enhanced behavioural and
neuroendocrine stress responses caused by early adversity. These
alterations may involve functional changes in medial prefrontal cortex
(mPFC), a region which modulates various stress responses.
Moreover, hemispheric specialisation may play a role in mPFC
function, such that the right hemisphere is preferentially involved in
mediating adaptive coping responses to stress. In the present study,
mPFC activity was examined in left and right hemispheres of adult
male Lister hooded rats subjected to MS (6 hrs/day on postnatal days
2-14), handling (H; 15 min/day) or animal facility rearing (AFR) as
pups. In vivo electrophysiology was used to record neuronal activity
under basal conditions and in response to FG-7142, a benzodiazepine
receptor inverse agonist which mimics behavioural and
neuroendocrine stress responses. Basal activity was attenuated by
MS compared to H and AFR, an effect which was lateralised to the
right hemisphere. Moreover, increased activity induced by FG-7142
was lateralised to different hemispheres in the early rearing groups.
FG-7142 increased left hemisphere activity in AFR and MS animals
(AFR>MS). Conversely, FG-7142 increased right hemisphere activity
in H animals. Thus, MS induces a lateralised deficit in mPFC function
which may model certain cognitive and affective disturbances
observed in psychiatric disorders associated with early adversity. The
effects of FG-7142 reported in H animals also add to evidence
suggesting increased resilience to the effects of stress in this group.
Supported by a Marie Curie Fellowship from the EU.
19.04
Basolateral amygdala aminergic transmission as a target of atypical
antipsychotic drug action
Glennon J C, Lewis L, Van der Kooij M A, Kleefstra A J, Tros R, Leguit, N,
Hamelink, R, McCreary, AC, Kruse, CK
1) Department of Chemistry, National University of Ireland Maynooth, Co.
Kildare, Ireland. 2) Solvay Pharmaceuticals Research Laboratories, Weesp,
1381CP, The Netherlands.
The basolateral amygdala (BLA) is part of a mesolimbic dopaminergic (DA)
circuit which may be hyperactive in psychosis. Changes in BLA DA and
noradrenaline (NA) transmission remain unstudied in animal models of
psychosis which encompass emotional and cognitive disturbance. Here,
the effect of the psychomimetic phencyclidine (PCP) alone and together
with the antipsychotics aripiprazole (ARI), clozapine (CLO) and haloperidol
(HAL), the partial D2 receptor agonist (-)-3PPP and the 5-HT1A receptor
agonist, 8-OH-DPAT were examined on BLA dialysate DA and NA levels.
Administration of PCP is associated with large sustained increases in
dialysate BLA DA and NA levels. Co-administration of ARI with PCP
reversed the PCP-induced increase in BLA dialysate DA and NA levels. In
contrast, co-administration with CLO or HAL with PCP failed to do this.
Interestingly, co-administration of (-)-3PPP with PCP could reverse the
PCP-mediated increase in NA but not DA levels while co-administration of
8-OH-DPAT with PCP could antagonise both the PCP mediated increase in
BLA DA and NA dialysate levels. Taken together, the data suggests that
BLA DA levels are elevated by PCP consistent with the DA hypothesis of
schizophrenia and the ability of ARI to reverse the PCP-induced increase in
BLA DA and NA may be 5-HT1A receptor mediated. The significance of the
PCP mediated increase in BLA NA levels and their reversal by both (-)-
3PPP and 8-OH-DPAT is deserving of further investigation but suggests
that both D2 partial and 5-HT1A agonists can regulate BLA NAergic tone
which may underlie emotion-related memory consolidation.
19.05
Comparing transient and persistent gamma oscillations in the rat
basolateral amygdala in vitro
Randall F E, Whittington M A, Cunningham M O
Newcastle University, School of Neurology, Neurobiology and
Psychiatry, Medical School, Framlington Place, Newcastle Upon Tyne
NE2 4HH
Oscillatory activity in the basolateral amygdala (BLA) is thought to
have an important role in the consolidation of emotional memories
(Pelletier and Paré, 2004). During emotional arousal the BLA has
been shown to produce gamma frequency oscillations (30-60 Hz) in
vivo (Pagano and Gault, 1964; Feschenko and Chilingaryan, 1990).
Understanding mechanisms by which oscillatory activity is generated
in the amygdala could identify how the amygdala communicates with
other brain areas in emotional situations. We previously reported a
model of transient gamma oscillations in the BLA in vitro evoked by
brief applications of L-glutamate (10 mM) in coronal slices (450μm) of
BLA from adult male Wistar rats. Here we report a persistent gamma
oscillation model evoked by bath application of Kainic acid (400nM).
The mean frequency of the persistent oscillation was 35 ± 1 Hz and
the mean power was 2030 ± 288 μV2/Hz. Pharmacological
investigation showed that, like the transient model, the network activity
underlying these oscillations was GABAA receptor-dependent but not
NMDA receptor-dependent. The persistent oscillations also showed
differential responses to AMPA/Kainate receptor antagonists different
to those previously seen in other brain areas including hippocampus.
Unlike the transient oscillations, the persistent oscillations were
abolished by gap junction blocker Octanol (1mM). The
pharmacological characteristics of the two models are similar and both
provide useful tools for characterizing the cell networks involved in
generating this activity.
Feschenko and Chilingaryan (1990) Neurosci. Behav. Physiol. 20:506-
13
Pagano and Gault (1964) Electroencephalogr. Clin. Neurophysiol.
17:255-60
Pelletier and Paré (2004) Biol. Psychiatry 55:559-62
19.06
Emotional responses to novelty and open spaces in a 3D maze: the
role of GABA-A and histamine H3 receptors
Ennaceur A (1), Michalikova S (1), Rensburg Rv (2), Curruthers N I (4),
Leurs R (3), Esch I (3), Chazot P L (2)
1.Sunderland Pharmacy School,Sunderland University,UK;Centre for
Integrative Neuroscience, Durham University;3Leiden-Amsterdam Center
for Drug Research, The Netherlands; 4.4Johnson & Johnson
Pharmaceutical Research and Development, San Diego, USA.
In the present study, we examined the behaviour of mice in our novel 3D
maze, composed of eight flexible arms radiating from a central platform.
Each arm can be manipulated independently and presented at the same,
below or above the level of a central platform. Mice need to cross a bridge
to reach flat, raised or elevated arms. Naïve mice were tested for the first
time in the raised arm configurations of the maze. This maze can also be
used to assess anxiety, learning and memory behaviours in an all-in-one
continuous system (see Ennaceur et al, this meeting). The effects of
different doses of GABA-A receptor selective compounds, chlordiazepoxide
and THIP, and H3R selective compounds methimepip (agonist) and JNJ-
5207852 (antagonist) have been explored on the behaviour of Balb/c mice.
This strain of mice has been previously shown to be more anxious than
C57 mice and less anxious than C3H mice2. An anxiolytic effect of the drug
is expected to align the behaviour of Balb/c to that of C57 mice, and an
anxiogenic effect of the drug would align the behaviour of Balb/c to that of
C3H mice. This model will be an ideal system to determine, for the first
time, the true role of the GABA-A and H3 receptors in bone fide ‘normal’
anxiety. We will present our early findings.
1. Ennaceur, A, Michalikova S, Chazot PL (2006a) Behav. Brain Res.171:
26–49.
2. Ennaceur, A, Michalikova S, van Rensburg, R, Chazot PL (2006b)
Behav. Brain Res 174: 9-38.
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