Neuroscience 2004 Abstract
| Presentation Number: | 620.15 |
|---|---|
| Abstract Title: | Blockade of anandamide degradation increases serotonergic neuron firing activity. |
| Authors: |
Gobbi, G.*1
; Bambico, F.1
; Piomelli, D.3
1Dept Psych, McGill Univ, Montreal, Canada 3Canada, 1033, Av. des Pins Ouest, H3A 1A1, |
| Primary Theme and Topics |
Synaptic Transmission and Excitability - Neurotransmitters -- Serotonin |
| Secondary Theme and Topics | Synaptic Transmission and Excitability<br />- Neurotransmitters<br />-- Cannabinoids |
| Session: |
620. Serotonin I Poster |
| Presentation Time: | Tuesday, October 26, 2004 10:00 AM-11:00 AM |
| Location: | San Diego Convention Center - Hall A-H, Board # H12 |
| Keywords: | CANNABINOIDS, ANTIDEPRESSANT, ANXIETY, FATTY ACID |
The active principle of marijuana, Δ9-tetrahydrocannabinol (THC), may regulate mood by hijacking an intrinsic cannabinoid-mediated mechanism involved in the control of emotions. In support of this hypothesis, pharmacological blockade of FAAH (fatty-acid amide hydrolase), an enzyme that hydrolyzes the endogenous cannabinoid anandamide, reduces anxiety-like behaviours in rats. These effects have not yet been identified, but they may involve activation of neurons in the dorsal raphe (DR) nucleus, a major source of serotonin in the mammalian brain. To test this possibility, we measured spontaneous firing activity in rats and mice DR neurons using in vivo recording techniques. Systemic administration of the potent and selective FAAH inhibitor URB597 (0.1 mg/kg, intravenous, i.v.) elicited a slow-onset increase in DR neuron firing, which became significant 20-140 min after drug injection (mean firing rate; vehicle: 1.45±0.1 Hz; URB597: 2.45±0.2 Hz; P < 0.01, n=55). This effect was prevented by the CB1 receptor antagonist rimonabant (SR141617A; 1 mg/kg) and was mimicked by the CB1 agonist WIN55212-2, which acted however immediately after administration. Subchronic treatment with URB597 (0.1 mg/kg, intravenous, i.v.; once daily for 4 days) resulted in a further elevation of spontaneous DR neuron activity (to 4.03±0.5 Hz; P < 0.01, n= 32), an effect that persisted for 8 hours after the last drug injection. To explore further the role of anandamide in the regulation of DR neuron activity, we used mice in which brain anandamide levels are elevated by genetic deletion of the faah gene. FAAH-/- mice displayed a DR firing rate of 3.3±0.1 Hz, which was significantly different from FAAH+/+ (1.8±0.3 Hz; n= 19). Noteworthy, the CB1 antagonist rimonabant partially normalized DR activity in these mutants. The results suggest that FAAH inhibitors, similarly to antidepressant drugs, enhance brain serotonergic transmission.
Sample Citation:
[Authors]. [Abstract Title]. Program No. XXX.XX. 2004 Neuroscience Meeting Planner. San Diego, CA: Society for Neuroscience, 2004. Online.
Copyright © 2004-2025 Society for Neuroscience; all rights reserved. Permission to republish any abstract or part of any abstract in any form must be obtained in writing by SfN office prior to publication.
