Modulation of Conditioned Fear, Fear-Conditioned Analgesia, and Brain Regional C-Fos Expression Following Administration of Muscimol into the Rat Basolateral Amygdala

Memory is measured by measuring retrieval. Retrieval is often triggered by the conditioned stimulus (CS); however, as known since Pavlov, presentation of the CS alone generates extinction. One-trial avoidance (IA) is a much used conditioned fear paradigm in which the CS is the safe part of a training apparatus, the unconditioned stimulus (US) is a footshock and the conditioned response is to stay in the safe area. In IA, retrieval is measured without the US, as latency to step-down from the safe area (i.e., a platform). Extinction is installed at the moment of the first unreinforced test session, as clearly shown by the fact that many drugs, including PKA, ERK and protein synthesis inhibitors as well as NMDA receptor antagonists, hinder extinction when infused into the hippocampus or the basolateral amygdala at the moment of the first test session but not later. Some, but not all the molecular systems required for extinction are also activated by retrieval, further endorsing the hypothesis that although retrieval is behaviorally and biochemically necessary for the generation of extinction, this last process constitutes a new learning secondary to the unreinforced expression of the original trace.

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Acute mitragynine administration suppresses cortical oscillatory power and systems theta coherence in rats

Journal of Psychopharmacology ◽

10.1177/0269881120914223 ◽

2020 ◽

Vol 34 (7) ◽

pp. 759-770

Author(s):

Rachel-Karson Thériault ◽

Joshua D Manduca ◽

Colin R Blight ◽

Jibran Y Khokhar ◽

Tariq A Akhtar ◽

...

Keyword(s):

Basolateral Amygdala ◽

Spectral Power ◽

Opioid Analgesic ◽

Field Potential ◽

Drug Effects ◽

Underlying Mechanism ◽

Oscillatory Activity ◽

Drug Induced ◽

Fos Expression ◽

Induced Changes

Background: Mitragynine is the major alkaloid of Mitragyna speciosa (kratom) with potential as a therapeutic in pain management and in depression. There has been debate over the potential side effects of the drug including addiction risk and cognitive decline. Aims: To evaluate the effects of mitragynine on neurophysiological systems function in the prefrontal cortex (PFC), cingulate cortex (Cg), orbitofrontal cortex, nucleus accumbens (NAc), hippocampus (HIP), thalamus (THAL), basolateral amygdala (BLA) and ventral tegmental area of rats. Methods: Local field potential recordings were taken from animals at baseline and for 45 min following mitragynine administration (10 mg/kg, intraperitoneally). Drug-induced changes in spectral power and coherence between regions at specific frequencies were evaluated. Mitragynine-induced changes in c-fos expression were also analyzed. Results: Mitragynine increased delta power and reduced theta power in all three cortical regions that were accompanied by increased c-fos expression. A transient suppression of gamma power in PFC and Cg was also evident. There were no effects of mitragynine on spectral power in any of the other regions. Mitragynine induced a widespread reduction in theta coherence (7–9 Hz) that involved disruptions in cortical and NAc connectivity with the BLA, HIP and THAL. Conclusions: These findings show that mitragynine induces frequency-specific changes in cortical neural oscillatory activity that could potentially impact cognitive functioning. However, the absence of drug effects within regions of the mesolimbic pathway may suggest either a lack of addiction potential, or an underlying mechanism of addiction that is distinct from other opioid analgesic agents.

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The Conditions under Which Consolidation of Serial-Order Conditioned Fear Requires De Novo Protein Synthesis in the Basolateral Amygdala Complex

Journal of Neuroscience ◽

10.1523/jneurosci.0768-19.2019 ◽

2019 ◽

Vol 39 (37) ◽

pp. 7357-7368 ◽

Cited By ~ 1

Author(s):

Matthew J. Williams-Spooner ◽

R. Frederick Westbrook ◽

Nathan M. Holmes

Keyword(s):

Protein Synthesis ◽

Basolateral Amygdala ◽

De Novo ◽

Conditioned Fear ◽

Serial Order ◽

De Novo Protein Synthesis

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Neuropeptide Y in the basolateral amygdala modulates the acquisition of conditioned fear

BMC Pharmacology ◽

10.1186/1471-2210-10-s1-a33 ◽

2010 ◽

Vol 10 (S1) ◽

Author(s):

Ramon O Tasan ◽

Dilip Verma ◽

Herbert Herzog ◽

Günther Sperk

Keyword(s):

Neuropeptide Y ◽

Basolateral Amygdala ◽

Conditioned Fear

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Effects of optogenetic photoexcitation of infralimbic cortex inputs to the basolateral amygdala on conditioned fear and extinction

Behavioural Brain Research ◽

10.1016/j.bbr.2020.112913 ◽

2021 ◽

Vol 396 ◽

pp. 112913

Author(s):

Olena Bukalo ◽

Mio Nonaka ◽

Chase A. Weinholtz ◽

Adriana Mendez ◽

William W. Taylor ◽

...

Keyword(s):

Basolateral Amygdala ◽

Conditioned Fear ◽

Infralimbic Cortex

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Pharmacological Blockade of PPAR Isoforms Increases Conditioned Fear Responding in the Presence of Nociceptive Tone

Molecules ◽

10.3390/molecules25041007 ◽

2020 ◽

Vol 25 (4) ◽

pp. 1007 ◽

Cited By ~ 1

Author(s):

Jessica C. Gaspar ◽

Bright N. Okine ◽

Alvaro Llorente-Berzal ◽

Michelle Roche ◽

David P. Finn

Keyword(s):

Conditioned Fear ◽

Intraperitoneal Administration ◽

Peroxisome Proliferator ◽

Sprague Dawley ◽

Intraplantar Injection ◽

Conditioned Analgesia ◽

Sprague Dawley Rats ◽

Pharmacological Blockade ◽

Peroxisome Proliferator Activated Receptors ◽

Nociceptive Behaviour

Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors with three isoforms (PPARα, PPARβ/δ, PPARγ) and can regulate pain, anxiety, and cognition. However, their role in conditioned fear and pain-fear interactions has not yet been investigated. Here, we investigated the effects of systemically administered PPAR antagonists on formalin-evoked nociceptive behaviour, fear-conditioned analgesia (FCA), and conditioned fear in the presence of nociceptive tone in rats. Twenty-three and a half hours following fear conditioning to context, male Sprague-Dawley rats received an intraplantar injection of formalin and intraperitoneal administration of vehicle, PPARα (GW6471), PPARβ/δ (GSK0660) or PPARγ (GW9662) antagonists, and 30 min later were re-exposed to the conditioning arena for 15 min. The PPAR antagonists did not alter nociceptive behaviour or fear-conditioned analgesia. The PPARα and PPARβ/δ antagonists prolonged context-induced freezing in the presence of nociceptive tone without affecting its initial expression. The PPARγ antagonist potentiated freezing over the entire trial. In conclusion, pharmacological blockade of PPARα and PPARβ/δ in the presence of formalin-evoked nociceptive tone, impaired short-term, within-trial fear-extinction in rats without affecting pain response, while blockade of PPARγ potentiated conditioned fear responding. These results suggest that endogenous signalling through these three PPAR isoforms may reduce the expression of conditioned fear in the presence of nociceptive tone.

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