Abstract
Background: Chronic mild stress (CMS) has been reported to induce behavioral abnormalities
that model human depression. To investigate the role in depression of phasic dopamine
transmission in cortical and limbic areas, we studied the effect of CMS on the responsiveness
of dopamine (DA) transmission to aversive and rewarding stimuli in rats by microdialysis
of the nucleus accumbens (NAc) shell and of the medial prefrontal cortex (PFCX).
Methods: Rats were subjected for 30 days to CMS and administered two trials of tail
pinch as aversive stimulus and two feeding sessions of a highly palatable food as
rewarding stimulus. Concentric microdialysis probes were implanted in the NAc shell
and in the medial PFCX.
Results: In unstressed rats, DA decreased in the NAc and increased in the PFCX on
the first tail-pinch trial; on the 1st feeding trial, DA increased in the NAc and to a larger extent in the PFCX. In the
second tail-pinch trial or feeding trial, these responses were maintained in the PFCX
but underwent habituation in the NAc. CMS did not affect basal dialysate DA in the
NAc or in the PFCX but influenced the responsiveness of DA transmission to tail pinches
and to feeding in a reciprocal manner. Thus, in the tail-pinch trial, CMS reversed
the inhibitory response of NAc DA transmission into a stimulatory one and potentiated
the stimulatory response in the PFCX. By contrast, in the feeding trial, CMS blunted
the stimulatory response of DA transmission in the NAc in the first trial and in the
PFCX in the second trial.
Conclusions: CMS reciprocally affected DA responsiveness to motivational stimuli,
facilitating or inducing a stimulatory DA response to aversive stimuli but blunting
stimulatory responses to rewarding stimuli. Given the postulated role of phasic DA
responsiveness in the NAc shell for learning and of DA transmission in the PFCX for
expression of motivation, we hypothesize that depression is the result of defective
learning and expression of aversive and appetitive motivation.
Keywords
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Article info
Publication history
Accepted:
August 16,
1999
Received in revised form:
August 6,
1999
Received:
May 21,
1999
Identification
Copyright
© 1999 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
