scholarly journals Scopolamine blocks context-dependent reinstatement of fear responses in rats

2021 ◽  
Author(s):  
Laura M. Vercammen ◽  
Adrian C. Lo ◽  
Rudi D’Hooge ◽  
Bram Vervliet
Keyword(s):  
Receptor Antagonist ◽  
Muscarinic Receptor ◽  
Experimental Research ◽  
Total Sample ◽  
Fear Memory ◽  
Systemic Administration ◽  
Female Rats ◽  
Acquisition Session ◽  
Return Of Fear ◽  
Context Dependent

AbstractReturn of fear poses a problem for extinction-based therapies of clinical anxiety. Experimental research has discovered several pathways to return of fear, one of which is known as reinstatement. Here, we evaluated in rats the potential of scopolamine, a non-selective muscarinic receptor antagonist that is also safe for use in humans, to prevent the reinstatement of extinguished fear. We conducted three experiments with a total sample of 96 female rats. All rats went through a fear acquisition session (tone-shock pairings, CS-US), followed by two extinction sessions (CS only) and a post-extinction fear memory test. Twenty-four hours later, rats were placed in the same or a different context from extinction and received two unsignaled foot shock (US) presentations. On the following day, CS-evoked freezing returned when the reinstating USs had occurred in the same context compared to a different context (context-dependent reinstatement, Experiment 1). Systemic administration of scopolamine before or after the reinstating USs blocked the return of CS-evoked freezing on the following day (Experiments 2 and 3). Our findings suggest that administering scopolamine around the time of an aversive experience could prevent relapse of extinguished fears in humans.

The (S)-(+)-enantiomer of dimethindene: a novel M2-selective muscarinic receptor antagonist

1995 ◽  
Vol 286 (3) ◽  
pp. 229-240 ◽  
Author(s):  
Otmar Pfaff ◽  
Caren Hildebrandt ◽  
Magali Waelbroeck ◽  
Xue Hou ◽  
Ulrich Moser ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Muscarinic Receptor ◽  
Muscarinic Receptor Antagonist

EXPRESS: Limitations of occasional reinforced extinction to alleviate spontaneous recovery and reinstatement effects: Evidence for a trial signalling mechanism

2021 ◽  
pp. 174702182110434
Author(s):  
María José Quintero ◽  
Amanda Flores ◽  
María Teresa Gutiérrez-Huerta ◽  
Patricia Molina-Guerrero ◽  
Francisco J López ◽  
...  
Keyword(s):  
Spontaneous Recovery ◽  
Fear Memory ◽  
Clinical Settings ◽  
Conditioning Procedure ◽  
Psychological Conditions ◽  
Return Of Fear ◽  
Promising Strategy ◽  
Potential Benefits ◽  
Theoretical Standpoint ◽  
Extinction Treatment

Fear extinction is not permanent but is instead more vulnerable than the original fear memory, as traditionally shown by the return of fear phenomena. Because of this, techniques to mitigate the return of fear are needed in the clinical treatment of related psychological conditions. One promising strategy is the occasional reinforced extinction treatment, introducing a gradual and sparse number of CS-US pairings within the extinction treatment. We present the results of three experiments in which we used a threat conditioning procedure in humans. Our main aim was to evaluate whether occasional reinforced extinction could reduce two different forms of relapse: spontaneous recovery (Experiments 1 and 2) and reinstatement (Experiment 3). Contrary to our predictions and previous literature, the results indicate that an occasional reinforcement treatment did not mitigate relapse compared with standard extinction. From a theoretical standpoint, these results are more consistent with the idea that extinction entails the acquisition of new knowledge than with the idea that there are conditions in which extinction leads to a weakening of the original fear memory. These findings also question the generality of the potential benefits of using occasional reinforced extinction in clinical settings.

M2-Receptor Subtype Does Not Mediate Muscarine-Induced Increases in [Ca2+]i in Nociceptive Neurons of Rat Dorsal Root Ganglia

2000 ◽  
Vol 84 (4) ◽  
pp. 1934-1941 ◽  
Author(s):  
Rainer Haberberger ◽  
Reas Scholz ◽  
Wolfgang Kummer ◽  
Michaela Kress
Keyword(s):  
Receptor Antagonist ◽  
Muscarinic Receptor ◽  
Sensory Neurons ◽  
Dorsal Root Ganglia ◽  
Dorsal Root ◽  
Receptor Subtype ◽  
Receptor Subtypes ◽  
Muscarinic Receptor Subtypes ◽  
Rt Pcr ◽  
Nociceptive Neurons

Multiple muscarinic receptor subtypes are present on sensory neurons that may be involved in the modulation of nociception. In this study we focused on the presence of the muscarinic receptor subtypes, M2 and M3 (M2R, M3R), in adult rat lumbar dorsal root ganglia (DRG) at the functional ([Ca2+]i measurement), transcriptional (RT-PCR), and translational level (immunohistochemistry). After 1 day in culture exposure of dissociated medium-sized neurons (20–35 μm diam) to muscarine was followed by rises in [Ca2+]i in 76% of the neurons. The [Ca2+]i increase was absent after removal of extracellular calcium and did not desensitize after repetitive application of the agonist. This rise in [Ca2+]i may be explained by the expression of M3R, which can induce release of calcium from internal stores via inositoltrisphospate. Indeed the effect was antagonized by the muscarinic receptor antagonist atropine as well as by the M3R antagonist, 4-diphenylacetoxy-N-(2 chloroethyl)-piperidine hydrochloride (4-DAMP). The pharmacological identification of M3R was corroborated by RT-PCR of total RNA and single-cell RT-PCR, which revealed the presence of mRNA for M3R in lumbar DRG and in single sensory neurons. In addition, RT-PCR also revealed the expression of M2R, which did not seem to contribute to the calcium changes since it was not prevented by the M2 receptor antagonist, gallamine. Immunohistochemistry demonstrated the presence of M2R and M3R in medium-sized lumbar DRG neurons that also coexpressed binding sites for the lectin I-B4, a marker for mainly cutaneous nociceptors. The occurrence of muscarinic receptors in putative nociceptive I-B4-positive neurons suggests the involvement of these acetylcholine receptors in the modulation of processing of nociceptive stimuli.

M1 and M3 muscarinic antagonists inhibit human nasal glandular secretion in vitro

1992 ◽  
Vol 73 (5) ◽  
pp. 2069-2073 ◽  
Author(s):  
J. Mullol ◽  
J. N. Baraniuk ◽  
C. Logun ◽  
M. Merida ◽  
J. Hausfeld ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Muscarinic Receptor ◽  
Enzyme Linked Immunosorbent Assay ◽  
Receptor Subtypes ◽  
Muscarinic Antagonists ◽  
Muscarinic Receptor Subtypes ◽  
Mucus Production ◽  
Glandular Secretion ◽  
M3 Receptor

Mucus glycoproteins (MGP) are high-molecular-weight glycoconjugates that are released from submucosal glands and epithelial goblet cells in the respiratory tract. Muscarinic receptors have an important role in the regulation of human nasal glandular secretion and mucus production, but it is not known which of the five muscarinic receptor subtypes are involved. The effect of nonselective and M1-, M2-, and M3-selective muscarinic antagonists on methacholine (MCh)-induced MGP secretion from human nasal mucosal explants was tested in vitro. MGP was assayed by enzyme-linked immunosorbent assay using a specific anti-MGP monoclonal antibody (7F10). MCh (100 microM) induced MGP secretion up to 127% compared with controls. MCh-induced MGP release was significantly inhibited by atropine (100 microM), the M, receptor antagonist pirenzepine (10–100 microM), and the M3 receptor antagonist 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP; 1–100 microM). 4-DAMP significantly inhibited MCh-induced MGP release at a lower concentration (1 microM) than pirenzepine (10 microM). The M2 receptor antagonists AF-DX 116 and gallamine (both at 100 microM) had no effect. No antagonist alone had a significant effect on MGP release. These results indicate that the M1 and M3 muscarinic receptor subtypes regulate MGP secretion from human nasal mucosa and suggest that the M3 receptor has the predominant effect.

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