NMDA receptor adjusted co-administration of ecstasy and cannabinoid receptor-1 agonist in the amygdala via stimulation of BDNF/Trk-B/CREB pathway in adult male rats.
Ghorbangol Ashabi, Mitra-Sadat Sadat-Shirazi, Solmaz Khalifeh, Laleh Elhampour, Mohammad-Reza Zarrindast
Brain Research Bulletin April 2017 DOI: 10.1016/j.brainresbull.2017.01.020 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical animal study Peer reviewed |
|---|---|
| Population | Male rats |
| Intervention | MDMA |
| Duration | Neuronal firing recorded 30 minutes after injections; amygdala collected 2 hours after drug injection |
| Topics | MDMA |
| Keywords | Amygdala Bdnf Creb Cannabinoid receptor-1 Nmda receptor |
| Key points | MDMA and/or ACPA reduced central amygdala firing rates dose-dependently versus sham, and ACPA plus MDMA increased BDNF, Trk-B, and CREB phosphorylation compared with MDMA alone. Adding the NMDA antagonist D-AP5 lowered these markers relative to ACPA plus MDMA, leading the authors to propose that NMDA receptors may mediate a protective effect of acute MDMA and ACPA co-injection through BDNF/Trk-B/CREB pathways. |
Abstract
Consumption of cannabinoid receptor-1 (CB-1) agonist such as cannabis is widely taken in 3,4- methylenedioxymethamphetamine (MDMA) or ecstasy users; it has been hypothesized that co-consumption of CB-1 agonist might protect neurons against MDMA toxicity. N-methyl-d-aspartate (NMDA) receptors regulate neuronal plasticity and firing rate in the brain through Tyrosine-kinase B (Trk-B) activation. The molecular and electrophysiological association among NMDA and MDMA/Arachidonylcyclopropylamide (ACPA, a selective CB-1 receptor agonist) co-consumption was not well-known. Here, neuronal spontaneous activity, Brain-derived neurotrophic factor (BDNF), Trk-B and cAMP response element binding protein (CREB) phosphorylation levels were recognized in ACPA and MDMA co-injected rats. Besides, we proved the role of NMDA receptor on MDMA and ACPA combination on neuronal spontaneous activity and Trk-B/BDNF pathway in the central amygdala (CeA). Male rats were anesthetized with intra-peritoneal injections of urethane; MDMA, D-2-amino-5-phosphonopentanoate (D-AP5, NMDA receptor antagonist) were injected into CeA. ACPA was administrated by intra-cerebroventricular injection. Thirty minutes following injections, neuronal firing rate was recorded from CeA. Two hours after drug injection, amygdala was collected from brain for molecular evaluations. Single administration of MDMA and/or ACPA reduced firing rates compared with sham group in the CeA dose-dependently. Injection of D-AP5, ACPA and MDMA reduced firing rate compared with sham group (P<0.001). Interestingly, injection of ACPA+MDMA enhanced BDNF, Trk-B and CREB phosphorylation compared with MDMA groups. D-AP5, ACPA and MDMA co-injection decreased BDNF, Trk-B and CREB phosphorylation levels compared with ACPA+MDMA in the amygdala (P<0.01). Probably, NMDA receptors are involved in the protective role of acute MDMA+ACPA co-injection via BDNF/Trk-B/CREB pathways.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
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and 12 more in the library