| Title |
2-AG promotes the expression of conditioned fear via cannabinoid receptor type 1 on GABAergic neurons
|
|---|---|
| Published in |
Psychopharmacology, March 2015
|
| DOI | 10.1007/s00213-015-3917-y |
| Pubmed ID | |
| Authors |
Alvaro Llorente-Berzal, Ana Luisa B. Terzian, Vincenzo di Marzo, Vincenzo Micale, Maria Paz Viveros, Carsten T. Wotjak |
| Abstract |
The contribution of two major endocannabinoids, 2-arachidonoylglycerol (2-AG) and anandamide (AEA), in the regulation of fear expression is still unknown. We analyzed the role of different players of the endocannabinoid system on the expression of a strong auditory-cued fear memory in male mice by pharmacological means. The cannabinoid receptor type 1 (CB1) antagonist SR141716 (3 mg/kg) caused an increase in conditioned freezing upon repeated tone presentation on three consecutive days. The cannabinoid receptor type 2 (CB2) antagonist AM630 (3 mg/kg), in contrast, had opposite effects during the first tone presentation, with no effects of the transient receptor potential vanilloid receptor type 1 (TRPV1) antagonist SB366791 (1 and 3 mg/kg). Administration of the CB2 agonist JWH133 (3 mg/kg) failed to affect the acute freezing response, whereas the CB1 agonist CP55,940 (50 μg/kg) augmented it. The endocannabinoid uptake inhibitor AM404 (3 mg/kg), but not VDM11 (3 mg/kg), reduced the acute freezing response. Its co-administration with SR141716 or SB366791 confirmed an involvement of CB1 and TRPV1. AEA degradation inhibition by URB597 (1 mg/kg) decreased, while 2-AG degradation inhibition by JZL184 (4 and 8 mg/kg) increased freezing response. As revealed in conditional CB1-deficient mutants, CB1 on cortical glutamatergic neurons alleviates whereas CB1 on GABAergic neurons slightly enhances fear expression. Moreover, 2-AG fear-promoting effects depended on CB1 signaling in GABAergic neurons, while an involvement of glutamatergic neurons remained inconclusive due to the high freezing shown by vehicle-treated Glu-CB1-KO. Our findings suggest that increased AEA levels mediate acute fear relief, whereas increased 2-AG levels promote the expression of conditioned fear primarily via CB1 on GABAergic neurons. |
X Demographics
The data shown below were collected from the profile of 1 X user who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Spain | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 111 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 1 | <1% |
| Unknown | 110 | 99% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 28 | 25% |
| Researcher | 20 | 18% |
| Student > Bachelor | 12 | 11% |
| Student > Doctoral Student | 8 | 7% |
| Student > Master | 7 | 6% |
| Other | 16 | 14% |
| Unknown | 20 | 18% |
| Readers by discipline | Count | As % |
|---|---|---|
| Agricultural and Biological Sciences | 29 | 26% |
| Neuroscience | 22 | 20% |
| Psychology | 11 | 10% |
| Pharmacology, Toxicology and Pharmaceutical Science | 7 | 6% |
| Medicine and Dentistry | 7 | 6% |
| Other | 8 | 7% |
| Unknown | 27 | 24% |
Attention Score in Context
This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 31 March 2015.
All research outputs
#14,225,412
of 22,805,349 outputs
Outputs from Psychopharmacology
#4,061
of 5,347 outputs
Outputs of similar age
#139,289
of 263,875 outputs
Outputs of similar age from Psychopharmacology
#24
of 46 outputs
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