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Cited by 68Neurotransmitter Receptor Influence on BehaviorMemory and Neural MechanismsStress Responses and Cortisol

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Impaired escape performance and enhanced conditioned fear in rats following exposure to an uncontrollable stressor are mediated by glutamate and nitric oxide in the dorsal raphe nucleus

Grahn, Ruth E, Watkins, Linda R, Maier, Steven F·2000·Behavioural Brain Research
DOI 10.1016/s0166-4328(00)00161-3
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Abstract

Exposure to uncontrollable aversive events produces a variety of behavioral consequences that do not occur if the aversive event is controllable. Accumulating evidence suggests that exaggerated excitation of serotonin (5-HT) neurons in the dorsal raphe nucleus (DRN) is sufficient to cause these same behaviors, such as poor shuttlebox escape performance and enhanced conditioned fear that occur 24 h after exposure to inescapable tailshock (IS). The aim of the present studies was to explore the possibility that N-methyl-D-aspartate (NMDA) receptor activation and nitric oxide (NO) formation within the DRN might be involved in mediating the behavioral consequences of IS. To this end, either the NMDA receptor antagonist 2-amino-5-phosphonovaleric acid (APV) or the nitric oxide synthase inhibitor Nw-nitro-L-arginine methyl ester (L-NAME), was microinjected into the DRN before IS or before testing 24 h later. Blocking NMDA receptors with APV in the DRN during IS prevented the usual impact of IS on escape responding and conditioned fear. However, injection of APV at the time of testing only reduced these effects. The DRN was shown to be the critical site mediating blockade of these behavioral changes since injection of APV lateral to the DRN did not alter the behavioral consequences of IS. Conversely, L-NAME was most effective in reversing the effects of IS when administered at the time of testing. These results suggest that there is glutamatergic input to the DRN at the time of IS th…

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  • Shuttlebox escape learning is very rapid; rodents escape with almost asymptotically fast latencies by the second or third trial.

    “it is learned very rapidly. Indeed, rodents escape with almost asymptotically fast latencies by the second or third trial (e.g., Grahn, Watkins, & Maier, 2000).”

    From Learned helplessness at fifty: Insights from neuroscience. (2016) · cites this paper as Grahn, Watkins, & Maier, 2000

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Metadata

Authors
Grahn, R. E., Watkins, L. R., & Maier, S. F.
Affiliations
  • Connecticut College (US)
  • University of Colorado Boulder (US)
Corresponding author
Grahn, Ruth E
ORCID
Maier, Steven F
Venue
Behavioural Brain Research
Publisher
Elsevier BV
Published
2000-07
Volume
112
Issue
1-2
Pages
33-41
ISSN
0166-4328 (ISSN-L)
DOI
10.1016/s0166-4328(00)00161-3
OpenAlex
W2045751028
Cited by
68
References
47
Citations by year
2025: 1 · 2023: 1 · 2020: 2 · 2019: 2 · 2018: 1 · 2017: 4 · 2016: 2 · 2015: 3 · 2014: 5 · 2013: 4 · 2012: 3
FWCI
1.29
Type
journal article
Language
en
Open access
closed
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Behavioural Brain Research (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Institute of Mental Health (MH-00314, MH 50479)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
Keywords
uncontrollable stress, dorsal raphe nucleus, serotonergic neurons, NMDA receptor, nitric oxide, glutamate, fear conditioning, escape behavior, APV, L-NAME, glutamatergic input, neuroplasticity
MeSH terms
Animals, Conditioning, Psychological, Electroshock, Enzyme Inhibitors, Escape Reaction, Fear, Helplessness, Learned, Male, Models, Neurological, Nitric Oxide, Random Allocation, Raphe Nuclei, Serotonin, 2-Amino-5-phosphonovalerate, Receptors, N-Methyl-D-Aspartate, Rats, Sprague-Dawley, Glutamic Acid, NG-Nitroarginine Methyl Ester, Rats

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