Role of the basolateral amygdala dopamine receptors in arachidonylcyclopropylamide-induced fear learning deficits

Nasehi, Mohammad; Hajian, Maryam; Ebrahimi-Ghiri, Mohaddeseh; Zarrindast, Mohammad‐Reza

doi:10.1007/s00213-015-4096-6

Cited by 24 publications

(21 citation statements)

References 56 publications

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“…It seems that the long-lasting delay in memory retrieval is due to learning deficit. Considerable evidence suggests that cannabinoid agonists can impair emotional (or aversive) as well as neutral (or rewarding) memory-related processes in a task-, region-, and memory stage-dependent manner (Ghiasvand et al, 2011;Nasehi et al, 2015a, Nasehi et al, 2015b, Nasehi et al, 2015d. This is consistent with other studies that have reported that exogenous acute cannabinoid treatment may have different outcomes depending on task aversiveness and the brain region involved (Abush and Akirav, 2010;De Oliveira Alvares et al, 2005;Ganon-Elazar and Akirav, 2009;Suzuki et al, 2004;Varvel et al, 2005).…”

Section: Discussionsupporting

confidence: 81%

Modulation of cannabinoid signaling by hippocampal 5-HT4 serotonergic system in fear conditioning

et al. 2016

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Behavioral studies have suggested a key role for the cannabinoid system in the modulation of conditioned fear memory. Likewise, much of the literature has revealed that the serotonergic system affects Pavlovian fear conditioning and extinction. A high level of functional overlap between the serotonin and cannabinoid systems has also been reported. To clarify the interaction between the hippocampal serotonin (5-HT4) receptor and the cannabinoid CB1 receptor in the acquisition of fear memory, the effects of 5-HT4 agents, arachidonylcyclopropylamide (ACPA; CB1 receptor agonist), and the combined use of these drugs on fear learning were studied in a fear conditioning task in adult male NMRI mice. Pre-training intraperitoneal administration of ACPA (0.1 mg/kg) decreased the percentage of freezing time in both context- and tone-dependent fear conditions, suggesting impairment of the acquisition of fear memory. Pre-training, intra-hippocampal (CA1) microinjection of RS67333, a 5-HT4 receptor agonist, at doses of 0.1 and 0.2 or 0.2 µg/mouse impaired contextual and tone fear memory, respectively. A subthreshold dose of RS67333 (0.005 µg/mouse) did not alter the ACPA response in either condition. Moreover, intra-CA1 microinjection of RS23597 as a 5-HT4 receptor antagonist did not alter context-dependent fear memory acquisition, but it did impair tone-dependent fear memory acquisition. However, a subthreshold dose of the RS23597 (0.01 µg/mouse) potentiated ACPA-induced fear memory impairment in both conditions. Therefore, we suggest that the blockade of hippocampal 5-HT4 serotonergic system modulates cannabinoid signaling induced by the activation of CB1 receptors in conditioned fear.

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Section: Discussionsupporting

confidence: 81%

Modulation of cannabinoid signaling by hippocampal 5-HT4 serotonergic system in fear conditioning

et al. 2016

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“…DA neurons originating in the VTA are known to be modulated by aversive stimuli, and have been implicated in fear conditioning and extinction (El-Ghundi, O'Dowd, and George 2001;Young, Joseph, and Gray 1993;Inoue et al 2000;Nader and LeDoux 1999;Guarraci and Kapp 1999;Holtzman-Assif, Laurent, and Westbrook 2010;Delgado et al 2008;Luo et al 2018;Salinas-Hernández et al 2018;Zweifel et al 2011;Pezze and Feldon 2004;Mueller, Bravo-Rivera, and Quirk 2010;Pignatelli et al 2017;Nasehi et al 2016;Pezze, Bast, and Feldon 2003;Budygin et al 2012;Robinson et al 2019;Lammel et al 2011;Jo, Heymann, and Zweifel 2018;Lutas et al 2019;Fadok, Dickerson, and Palmiter 2009;Groessl et al 2018;Bouchet et al 2018;Wenzel et al 2018;Wang and Tsien 2011;Mileykovskiy and Morales 2011) . However, it was unclear if and how neural correlates of fear extinction are topographically organized within the VTA.…”

Section: Discussionmentioning

confidence: 99%

Distinct signals in medial and lateral VTA dopamine neurons modulate fear extinction at different times

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Gundersen

et al. 2020

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Dopamine (DA) neurons are known to encode reward prediction error (RPE), in addition to other signals, such as salience. While RPE is known to support learning, the role of salience in supporting learning remains less clear. To address this, we recorded and manipulated VTA DA neurons in mice during fear extinction, a behavior we observed to generate spatially segregated RPE and salience signals. We applied deep learning to classify mouse freezing behavior, eliminating the need for human scoring. Our fiber photometry recordings showed that DA neurons in medial and lateral VTA have distinct activity profiles during fear extinction: medial VTA activity more closely reflected RPE, while lateral VTA activity more closely reflected a salience-like signal. Optogenetic inhibition of DA neurons in either region slowed fear extinction, with the relevant time period for inhibition differing across regions. Our results indicate that salience-like signals can have similar downstream consequences to RPE-like signals, although with different temporal dependencies.

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“…The objective of the present investigation was to evaluate the role of BLA serotonin 5-HT4 receptors in fear memory responses induced by the activation of cannabinoid CB1 receptors in mice. In so doing, we examined (1) freezing behavior as a defensive behavior expressed by rodents in fearful situations, which is defined by immobility in a stereotyped crouching position (Blanchard and Blanchard, 1969;Nasehi et al, 2015a), (2) latency to the freezing which is the delay time to the first freezing behavior (Nasehi et al, 2015a), (3) Selfgrooming behavior whose occurrence is influenced by emotional factors and is observed during (and following) exposure to different types of stressful situations/stimuli (Estanislau et al, 2013) and, (4) rearing behavior which is determined by emotionality and also reflects reaction to novelty (Borta and Schwarting, 2005). Since freezing behavior is the main factor to evaluate fear memory, we will discuss this factor more comprehensively.…”

Section: Discussionmentioning

confidence: 99%

Interplay between serotonin and cannabinoid function in the amygdala in fear conditioning

et al. 2016

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The possible interactions between the cannabinoid and serotonin systems in the regions of the brain involved in emotional learning and memory formation have been studied by some researchers. In view of the key role of the amygdala in the acquisition and expression of fear memory, we investigated the involvement of basolateral amygdala (BLA) serotonin 5-HT4 receptors in arachidonylcyclopropylamide (ACPA; selective CB1 cannabinoid receptor agonist)-induced fear memory consolidation impairment. In our study, a context and tone fear conditioning apparatus was used for testing fear conditioning in adult male NMRI mice. The results showed that intraperitoneal administration of ACPA 0.5 or 0.05, 0.1 and 0.5mg/kg immediately after training decreased the percentage of freezing time in context or tone fear conditioning respectively, suggesting a context- or tone-dependent fear memory consolidation impairment. Post-training intra-BLA microinjections of RS67333, as 5-HT4 serotonin receptor agonist, at doses of 0.025 and 0.05 µg/mouse also impaired context or tone memory consolidation, while RS23597, as 5-HT4 serotonin receptor antagonist, did not produce a marked difference in both fear memories as compared with the control group. Moreover, a subthreshold dose of RS67333 did not alter ACPA response in both fear conditionings. Interestingly, a subthreshold dose of RS23597 potentiated or reversed ACPA response at the dose of 0.01 or 0.05 respectively. It is concluded that BLA serotonin 5-HT4 receptors are involved in tone-dependent fear memory consolidation impairment induced by CB1 activation using ACPA, suggesting a modulatory role for serotonin 5-HT4 receptor.

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Role of the basolateral amygdala dopamine receptors in arachidonylcyclopropylamide-induced fear learning deficits

Cited by 24 publications

References 56 publications

Modulation of cannabinoid signaling by hippocampal 5-HT4 serotonergic system in fear conditioning

Modulation of cannabinoid signaling by hippocampal 5-HT4 serotonergic system in fear conditioning

Distinct signals in medial and lateral VTA dopamine neurons modulate fear extinction at different times

Interplay between serotonin and cannabinoid function in the amygdala in fear conditioning

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