The endocannabinoid system: An emotional buffer in the modulation of memory function

Morena, Maria; Campolongo, Patrizia

doi:10.1016/j.nlm.2013.12.010

Cited by 124 publications

(90 citation statements)

References 198 publications

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“…We recently reported that the level of emotional arousal at the time of training is an important factor in determining cannabinoid effects on memory (13): WIN55,212-2 administration enhanced long-term object recognition memory when rats were trained under a high arousal condition but was ineffective with low-arousing training (13). Although the findings of our prior studies, as well as those of other investigators (6,8,(11)(12)(13), indicate that administration of cannabinoids can modulate memory consolidation, studies have not yet investigated whether AEA or 2-AG are released physiologically in response to emotionally arousing training and normally play a role in creating strong memories for these experiences. The present experiments investigated this issue.…”

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confidence: 51%

“…In addition, there is extensive evidence that the basolateral complex of the amygdala (BLA), hippocampus, and medial prefrontal cortex (mPFC) are all crucially involved in mediating emotional arousal effects on memory consolidation (2,3). The consolidation of memories of arousing experiences requires an orchestration of neural activity in these brain systems, and the cannabinoid system has emerged as a key modulator of such function (1,(4)(5)(6). Endogenous cannabinoid ligands [termed endocannabinoids, mainly N-arachidonoyl ethanolamine (anandamide; AEA) and 2-arachidonoyl glycerol (2-AG)] are released from postsynaptic membranes and feedback in a retrograde manner onto either excitatory or inhibitory presynaptic terminals, thus suppressing both excitatory and inhibitory signaling within specific neuronal circuits (7).…”

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confidence: 99%

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Endogenous cannabinoid release within prefrontal-limbic pathways affects memory consolidation of emotional training

Morena

Roozendaal

Trezza

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Previous studies have provided extensive evidence that administration of cannabinoid drugs after training modulates the consolidation of memory for an aversive experience. The present experiments investigated whether the memory consolidation is regulated by endogenously released cannabinoids. The experiments first examined whether the endocannabinoids anandamide (AEA) and 2-arachidonoyl glycerol (2-AG) are released by aversive training. Inhibitory avoidance training with higher footshock intensity produced increased levels of AEA in the amygdala, hippocampus, and medial prefrontal cortex (mPFC) shortly after training in comparison with levels assessed in rats trained with lower footshock intensity or unshocked controls exposed only to the training apparatus. In contrast, 2-AG levels were not significantly elevated. The additional finding that posttraining infusions of the fatty acid amide hydrolase (FAAH) inhibitor URB597, which selectively increases AEA levels at active synapses, administered into the basolateral complex of the amygdala (BLA), hippocampus, or mPFC enhanced memory strongly suggests that the endogenously released AEA modulates memory consolidation. Moreover, in support of the view that this emotional training-associated increase in endocannabinoid neurotransmission, and its effects on memory enhancement, depends on the integrity of functional interactions between these different brain regions, we found that disruption of BLA activity blocked the training-induced increases in AEA levels as well as the memory enhancement produced by URB597 administered into the hippocampus or mPFC. Thus, the findings provide evidence that emotionally arousing training increases AEA levels within prefrontallimbic circuits and strongly suggest that this cannabinoid activation regulates emotional arousal effects on memory consolidation.anandamide | endocannabinoids | cannabinoid receptors | inhibitory avoidance | emotional arousal

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confidence: 51%

mentioning

confidence: 99%

Endogenous cannabinoid release within prefrontal-limbic pathways affects memory consolidation of emotional training

Morena

Roozendaal

Trezza

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

122

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“…Emotional homeostasis was explained as "avoiding excesses and deficiencies" (Marco and Viveros 2009), "an appropriate reaction to stressful events" (Ruehle et al 2012), and as "an emotional buffer" (Morena and Campolongo 2014). Active coping on its turn is an extreme of a continuum (the other extreme being passive coping), and may not always constitute an "appropriate response" (Koolhaas et al 1999).…”

Section: Cannabinoids and Copingmentioning

confidence: 99%

“…Moreira and Lutz (2008) identified three reasons for discrepant behavioral findings: the 'on demand' nature of endocannabinoid synthesis and release, which makes effects dependent on both environmental stimuli and internal emotional states; the wide distribution of cannabinoid receptors by which the system modulates brain regions with different functions; and finally, effects of cannabinoids on other neurotransmitters, which have opposing effects on behavior. The idea emerging from this concept is that endocannabinoids maintain emotional homeostasis by controlling neuronal excitability and by buffering the effects of environmental context and stress which may have variable consequences in particular behavioral tests (Haj-Dahmane and Shen 2011;Marco and Viveros 2009;Moreira and Lutz 2008;Morena and Campolongo 2014;Ruehle et al 2012).…”

Section: Introductionmentioning

confidence: 99%

The effects anandamide signaling in the prelimbic cortex and basolateral amygdala on coping with environmental stimuli in rats

et al. 2016

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RATIONALE: Several lines of recent evidence suggest that endocannabinoids affect behavior by influencing the general patterns of challenge responding. OBJECTIVES: Here we investigated the brain mechanisms underlying this phenomenon in rats. METHODS: The anandamide hydrolysis inhibitor URB597 was condensed into the tip of stainless steel cannulae, which were chronically implanted slightly above the prelimbic cortex (PRL) or the basolateral amygdala (BLA), two important regions of coping and endocannabinoid action. Thereafter we investigated behavioral responsiveness to ambient light level in the elevated plus-maze and conditioned fear tests. RESULTS: URB597 concentration was ~30 μg/mg protein in target areas; local brain anandamide levels increased threefold, without significant changes in 2-arachidonoylglycerol.High levels of illumination halved the time spent by controls in the open arms of the plus-maze.No similar decrease was observed in rats with URB597 implants in the PRL. High light decreased conditioned fear by 30% in controls, but not in rats with prelimbic URB597 implants.Unresponsiveness to environmental challenges was not attributable to the anxiolytic effects of anandamide enhancement, as implants induced paradoxical anxiogenic-like effects under low light, which could be explained by effects on stimulus responsiveness rather than by effects on anxiety.URB597 implants targeting the BLA did not affect stimulus responsiveness. CONCLUSIONS:Our findings show that elevated prelimbic anandamide signaling leads to less environmentdependent (more autonomous) behavioral responses to challenges, which is an attribute of active coping styles. These findings are discussed in light of two emerging concepts of endocannabinoid roles, particularly "emotional homeostasis" and "active coping".

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“…Nowadays, researchers are focused on the development of new potential anticonvulsants that also protect neurons against degeneration [15][16][17][18]. In searching for the best neurological drug protecting neuronal cells, stimulating neurogenesis, but also without developing side-effects, cannabinoids have proved to be a strong group of substances with many beneficial properties [19][20][21][22][23][24][25].…”

Section: Introductionmentioning

confidence: 99%

Increased neurogenesis after ACEA and levetiracetam treatment in mouse pilocarpine model of epilepsy

Zagaja¹,

Szewczyk²,

Haratym-Maj³

et al. 2017

J Pre Clin Clin Res.

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Introduction and objectives. The aim of the study was to asses the impact of long-term therapy with the second generation antiepileptic drug levetiracetam (LEV) with arachidonyl-2'-chloroethylamide (ACEA), a highly selective cannabinoid CB1 receptor agoniston the process of neurogenesis in a mouse pilocarpine model of epilepsy (PILO). Additionally, a relationship was established between the treatment with ACEA in combination with LEV, and hippocampal neurogenesis in mouse PILO brain. Materials and method. All experiments were performed on adolescent male CB57/BL mice injected i.p. with LEV (10 mg/kg), ACEA (10 mg/kg) and PMSF (30 mg/kg) (phenylmethylsulfonyl fluoride -a substance protecting ACEA against degradation by the fatty-acid amidohydrolase), pilocarpine (PILO, a single dose 290 mg/kg) and methylscopolamine (30 min before PILO to stop the peripheral cholinergic effects of the pilocarpine, 1 mg/kg). The process of neurogenesis was evaluated after10 days treatment with LEV and ACEA. Results. Obtained results indicated that the combinations of ACEA+PMSF+LEV and ACEA +PMSF increased the total number of total newborn cells compared to the control. Moreover, ACEA+PMSF administered alone and in combination with LEV had a significant impact on neurogenesis increasing the total number of newborn neurons compared to the control group. Neither LEV nor PMSF had a significant impact on the number of proliferating cells and newborn neurons when compared to the control PILO group. In turn, LEV administered alone decreased significantly the number of astrocytes. However, ACEA+PMSF has demonstrated significant increase of astrocytes compare to control mice. Conclusions. These data provide substantial evidence that the combination of LEV+ACEA significantly increases the level of newborn neurons in the PILO dentate subgranular zone.

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The endocannabinoid system: An emotional buffer in the modulation of memory function

Cited by 124 publications

References 198 publications

Endogenous cannabinoid release within prefrontal-limbic pathways affects memory consolidation of emotional training

Endogenous cannabinoid release within prefrontal-limbic pathways affects memory consolidation of emotional training

The effects anandamide signaling in the prelimbic cortex and basolateral amygdala on coping with environmental stimuli in rats

Increased neurogenesis after ACEA and levetiracetam treatment in mouse pilocarpine model of epilepsy

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