scholarly journals Propofol Enhances Memory Formation via  an Interaction with the Endocannabinoid System

2011 ◽  
Vol 114 (6) ◽  
pp. 1380-1388 ◽  
Author(s):  
Daniela Hauer ◽  
Patrizia Ratano ◽  
Maria Morena ◽  
Sergio Scaccianoce ◽  
Isabel Briegel ◽  
...  
Keyword(s):  
Memory Consolidation ◽  
Acid Amide ◽  
Avoidance Performance ◽  
Endocannabinoid System ◽  
Inhibitory Avoidance ◽  
Dark Compartment ◽  
Vehicle Group ◽  
Stressful Event ◽  
Avoidance Task ◽  
General Anesthetics

Background Propofol is associated with postoperative mood alterations and induces a higher incidence of dreaming compared with other general anesthetics. These effects might be mediated by propofol's inhibitory action on fatty acid amide hydrolase, the enzyme that degrades the endocannabinoid anandamide. Because propofol is also associated with a higher incidence of traumatic memories from perioperative awareness and intensive care unit treatment and the endocannabinoid system is involved in regulating memory consolidation of emotional experiences, the authors investigated whether propofol, at anesthetic doses, modulates memory consolidation via an activation of the endocannabinoid system. Methods Male Sprague-Dawley rats were trained on an inhibitory avoidance task in which they received an inescapable foot shock upon entering the dark compartment of the apparatus. Drugs were administered intraperitoneally immediately or 30, 90, or 180 min after training. On the retention test 48 h later, the latency to reenter the dark compartment was recorded and taken as a measure of memory retention. Results The anesthetic doses of propofol administered after training significantly increased latencies of 48-h inhibitory avoidance performance (483.4 ± 181.3, 432.89 ± 214.06, 300 and 350 mg/kg, respectively; mean ± SD) compared with the corresponding vehicle group (325.33 ± 221.22, mean ± SD), which is indicative of stronger memory consolidation in propofol treated rats. Administration of a nonimpairing dose of the cannabinoid receptor antagonist rimonabant blocked the memory enhancement induced by propofol (123.39 ± 133.10, mean ± SD). Delayed administration of propofol 90 and 180 min after training or immediate posttraining administration of the benzodiazepine midazolam or the barbiturate pentobarbital did not significantly alter retention. Conclusions These findings indicate that propofol, in contrast to other commonly used sedatives, enhances emotional memory consolidation when administered immediately after a stressful event by enhancing endocannabinoid signaling.

scholarly journals Additive effect of harmane and muscimol for memory consolidation impairment in inhibitory avoidance task

Neuroscience ◽  
2016 ◽  
Vol 339 ◽  
pp. 287-295 ◽  
Author(s):  
Mohammad Nasehi ◽  
Parastoo Morteza-zadeh ◽  
Fatemeh Khakpai ◽  
Mohammad-Reza Zarrindast
Keyword(s):  
Memory Consolidation ◽  
Inhibitory Avoidance ◽  
Additive Effect ◽  
Avoidance Task ◽  
Inhibitory Avoidance Task

scholarly journals A Mixed Glucocorticoid/Mineralocorticoid Selective Modulator With Dominant Antagonism in the Male Rat Brain

Endocrinology ◽  
2015 ◽  
Vol 156 (11) ◽  
pp. 4105-4114 ◽  
Author(s):  
Erika Atucha ◽  
Ioannis Zalachoras ◽  
José K. van den Heuvel ◽  
Lisa T. C. M. van Weert ◽  
Diana Melchers ◽  
...  
Keyword(s):  
Memory Consolidation ◽  
Glucocorticoid Receptors ◽  
Target Genes ◽  
Inhibitory Avoidance ◽  
Male Rat ◽  
Molecular Profile ◽  
Avoidance Task ◽  
Antagonistic Effects ◽  
Acute And Chronic Stress

Adrenal glucocorticoid hormones are potent modulators of brain function in the context of acute and chronic stress. Both mineralocorticoid (MRs) and glucocorticoid receptors (GRs) can mediate these effects. We studied the brain effects of a novel ligand, C118335, with high affinity for GRs and modest affinity for MRs. In vitro profiling of receptor-coregulator interactions suggested that the compound is a “selective modulator” type compound for GRs that can have both agonistic and antagonistic effects. Its molecular profile for MRs was highly similar to those of the full antagonists spironolactone and eplerenone. C118335 showed predominantly antagonistic effects on hippocampal mRNA regulation of known glucocorticoid target genes. Likewise, systemic administration of C118335 blocked the GR-mediated posttraining corticosterone-induced enhancement of memory consolidation in an inhibitory avoidance task. Posttraining administration of C118335, however, gave a strong and dose-dependent impairment of memory consolidation that, surprisingly, reflected involvement of MRs and not GRs. Finally, C118335 treatment acutely suppressed the hypothalamus-pituitary-adrenal axis as measured by plasma corticosterone levels. Mixed GR/MR ligands, such as C118335, can be used to unravel the mechanisms of glucocorticoid signaling. The compound is also a prototype of mixed GR/MR ligands that might alleviate the harmful effects of chronic overexposure to endogenous glucocorticoids.

Effects of General Anesthesia on Anandamide Blood Levels in Humans

2006 ◽  
Vol 104 (2) ◽  
pp. 273-277 ◽  
Author(s):  
Gustav Schelling ◽  
Daniela Hauer ◽  
Shahnaz Christina Azad ◽  
Martin Schmoelz ◽  
Alexander Chouker ◽  
...  
Keyword(s):  
Fatty Acid ◽  
General Anesthesia ◽  
Repeated Measures ◽  
Fatty Acid Amide Hydrolase ◽  
Acid Amide ◽  
Endocannabinoid System ◽  
Blood Levels ◽  
General Anesthetics ◽  
Amide Hydrolase ◽  
Fatty Acid Amide

Background The endocannabinoid system includes G-protein-coupled cannabinoid receptors, the endocannabinoids N-arachidonoylethanolamine (anandamide) and 2-arachidonoylglycerol, and multiple enzymes involved in the biosynthesis and degradation of endocannabinoids, including the anandamide metabolizing enzyme fatty acid amide hydrolase. Endocannabinoids play an important role in the physiologic control of sleep, pain processing, and emesis. The authors therefore investigated the effects of general anesthesia on the endocannabinoid system in humans. Methods The authors measured whole blood levels of anandamide in 12 patients after induction of general anesthesia with etomidate (an agent shown to have no effect on anandamide levels) and maintenance of anesthesia with the volatile agent sevoflurane as well as in 12 patients undergoing total intravenous anesthesia with propofol, a known inhibitor of fatty acid amide hydrolase in the mouse brain. Anandamide levels were measured using high-performance liquid chromatography-tandem mass spectrometry at four time points (before and at 10, 20, 30, and 40 min after induction of anesthesia). Results Patients of the sevoflurane group showed a significant decline in anandamide levels from induction of anesthesia to 40 min after induction, whereas anandamide levels in patients of the propofol group remained unchanged (type III sum of squares = 1725.66, F = 162.60, P < 0.001, repeated-measures analysis of variance). Conclusion General anesthesia influences the endocannabinoid system in a drug-dependent way, which may explain side effects of general anesthetics such as psychomimetic and antiemetic properties of propofol and the high incidence of postoperative nausea and vomiting after volatile anesthetics. These findings suggest new targets for anesthetic drug development.

Histamine infused into basolateral amygdala enhances memory consolidation of inhibitory avoidance

2013 ◽  
Vol 16 (7) ◽  
pp. 1539-1545 ◽  
Author(s):  
Fernando Benetti ◽  
Ivan Izquierdo
Keyword(s):  
Receptor Antagonist ◽  
Memory Consolidation ◽  
Receptor Agonist ◽  
Basolateral Amygdala ◽  
Inhibitory Avoidance ◽  
Avoidance Task ◽  
H1 Receptor ◽  
H3 Receptor ◽  
H2 Antagonist

Abstract The role of the basolateral amygdala (BLA) in the consolidation of aversive memory is well established. Here we investigate the involvement of the histaminergic system in BLA on this variable. Rats were chronically implanted with bilateral cannulae in the BLA and after recovery were trained in a one-trial step-down inhibitory avoidance task. Immediately after training histaminergic compounds either alone or in combination were infused through the cannulae. Memory was assessed in test sessions carried out 24 h after the training session. Post-training histamine (1–10 nmol; 0.5 µl/side) enhanced consolidation and the histamine H3 receptor antagonist thioperamide (50 nmol; 0.5 µl/side) impaired memory consolidation. The effect was shared by the histamine N-methyltransferase inhibitor SKF-91844 (50 nmol; 0.5 µl/side) as well as by the H3 receptor agonist imetit (10 nmol; 0.5 µl/side). The promnesic action of histamine was unaffected by the H1 receptor antagonist pyrilamine (50 nmol; 0.5 µl/side). The H1 receptor agonist pyridylethylamine (10 nmol; 0.5 µl/side), the H2 agonist dimaprit (10 nmol; 0.5 µl/side) and the H2 antagonist ranitidine (50 nmol; 0.5 µl/side) were ineffective. Histaminergic compounds infused into the BLA had no effect on open-field or elevated plus-maze behaviour. The data show that histamine induces a dose-dependent mnemonic effect in rats and indicate that this reflects a role of endogenous histamine in the BLA mediated by H3 receptors.

scholarly journals Elevated Brain Fatty Acid Amide Hydrolase Induces Depressive-Like Phenotypes in Rodent Models: A Review

2021 ◽  
Vol 22 (3) ◽  
pp. 1047
Author(s):  
Dorsa Rafiei ◽  
Nathan J. Kolla
Keyword(s):  
Depressive Symptoms ◽  
Fatty Acid ◽  
Animal Models ◽  
Fatty Acid Amide Hydrolase ◽  
Acid Amide ◽  
Endocannabinoid System ◽  
Animal Models Of Depression ◽  
Amide Hydrolase ◽  
Fatty Acid Amide

Altered activity of fatty acid amide hydrolase (FAAH), an enzyme of the endocannabinoid system, has been implicated in several neuropsychiatric disorders, including major depressive disorder (MDD). It is speculated that increased brain FAAH expression is correlated with increased depressive symptoms. The aim of this scoping review was to establish the role of FAAH expression in animal models of depression to determine the translational potential of targeting FAAH in clinical studies. A literature search employing multiple databases was performed; all original articles that assessed FAAH expression in animal models of depression were considered. Of the 216 articles that were screened for eligibility, 24 articles met inclusion criteria and were included in this review. Three key findings emerged: (1) FAAH expression is significantly increased in depressive-like phenotypes; (2) genetic knockout or pharmacological inhibition of FAAH effectively reduces depressive-like behavior, with a dose-dependent effect; and (3) differences in FAAH expression in depressive-like phenotypes were largely localized to animal prefrontal cortex, hippocampus and striatum. We conclude, based on the animal literature, that a positive relationship can be established between brain FAAH level and expression of depressive symptoms. In summary, we suggest that FAAH is a tractable target for developing novel pharmacotherapies for MDD.

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