Crestani et al. Behavioral and Brain Functions 2010, 6:30
http://www.behavioralandbrainfunctions.com/content/6/1/30
Open Access RESEARCH
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Research
Acute reversible inactivation of the bed nucleus of
stria terminalis induces antidepressant-like effect
in the rat forced swimming test
Carlos C Crestani
1
, Fernando HF Alves
1
, Fernando MA Correa
1
, Francisco S Guimarães
1
and Sâmia RL Joca*
2
Abstract
Background: The bed nucleus of stria terminalis (BNST) is a limbic forebrain structure involved in hypothalamo-
pituitary-adrenal axis regulation and stress adaptation. Inappropriate adaptation to stress is thought to compromise
the organism's coping mechanisms, which have been implicated in the neurobiology of depression. However, the
studies aimed at investigating BNST involvement in depression pathophysiology have yielded contradictory results.
Therefore, the objective of the present study was to investigate the effects of temporary acute inactivation of synaptic
transmission in the BNST by local microinjection of cobalt chloride (CoCl
2
) in rats subjected to the forced swimming
test (FST ).
Methods: Rats implanted with cannulae aimed at the BNST were submitted to 15 min of forced swimming (pretest).
Twenty-four hours later immobility time was registered in a new 5 min forced swimming session (test). Independent
groups of rats received bilateral microinjections of CoCl
2
(1 mM/100 nL) before or immediately after pretest or before
the test session. Additional groups received the same treatment and were submitted to the open field test to control
for unspecific effects on locomotor behavior.
Results: CoCl
2
injection into the BNST before either the pretest or test sessions reduced immobility in the FST,
suggesting an antidepressant-like effect. No significant effect of CoCl
2
was observed when it was injected into the
BNST immediately after pretest. In addition, no effect of BNST inactivation was observed in the open field test.
Conclusion: These results suggest that acute reversible inactivation of synaptic transmission in the BNST facilitates
adaptation to stress and induces antidepressant-like effects.
Background
The bed nucleus of stria terminalis (BNST) is a limbic
forebrain structure situated ventrally to the lateral septal
nucleus and dorsally to the preoptic area of the hypothal-
amus [1,2]. It has extensive reciprocal connections with
other limbic structures as well as with brainstem auto-
nomic nuclei [2-5], and it is an import relay station for the
integration of information from brain regions associated
with the control of emotional, cognitive, autonomic,
endocrine and behavioral responses [2,6-13].
Several studies have suggested that the BNST mediates
behavioral responses to acute and chronic aversive stim-
uli [5,14]. This is supported by reports that the BNST is
activated in response to stress [15-18] and modulates
anxiety-related behaviors in several animal models
[5,10,19,20]. Moreover, the BNST could also mediate
behavioral adaptation to chronic stress exposure [21-24].
Inappropriate adaptation to stress is thought to compro-
mise the organism's coping mechanisms, which have
been implicated in the etiology of stress-related disor-
ders, such as posttraumatic stress disorder (PTSD) and
depression [25-27].
BNST involvement in the activation and termination of
the hypothalamo-pituitary-adrenal (HPA) axis response
to stress has been well documented in the literature [6,28-
30]. Activation of the HPA axis is a primary mechanism
* Correspondence: samia@usp.br
2
Laboratory of Pharmacology, Department of Physics and Chemistry, School of
Pharmaceutical Sciences of Ribeirão Preto; University of São Paulo, 14040-903,
Ribeirão Preto, SP, Brazil
Full list of author information is available at the end of the article