Publication details
2-AG promotes the expression of conditioned fear via cannabinoid receptor type 1 on GABAergic neurons
| Authors | |
|---|---|
| Year of publication | 2015 |
| Type | Article in Periodical |
| Magazine / Source | Psychopharmacology |
| MU Faculty or unit | |
| Citation | |
| Web | http://download.springer.com/static/pdf/322/art%253A10.1007%252Fs00213-015-3917-y.pdf?originUrl=http%3A%2F%2Flink.springer.com%2Farticle%2F10.1007%2Fs00213-015-3917-y&token2=exp=1447855112~acl=%2Fstatic%2Fpdf%2F322%2Fart%25253A10.1007%25252Fs00213-015-39 |
| Doi | http://dx.doi.org/10.1007/s00213-015-3917-y |
| Field | Neurology, neurosurgery, neurosciences |
| Keywords | Fear extinction; TRPV1; CB1; CB2; URB597; JZL184; AM404; Anandamide |
| Description | 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 mu g/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. |
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