Neuroscience 2005 Abstract
| Presentation Number: | 563.10 |
|---|---|
| Abstract Title: | Altered cerebellar synaptic activity following chronic Δ9-THC exposure. |
| Authors: |
Tonini, R.*1
; Ciardo, S.1
; Cerovic, M.1
; Rubino, T.2
; Parolaro, D.2
; Mazzanti, M.1
; Zippel, R.3
1Dept of Cellular and Developmental Biology, Univ. La Sapienza, Roma, Italy 2Italy, P.le Aldo Moro 5, 00185, 3DBSF, P.le Aldo Moro 5, 00185, |
| Primary Theme and Topics |
Disorders of the Nervous System - Addiction and Drugs of Abuse -- Cannabinoids |
| Secondary Theme and Topics | Neural Excitability, Synapses, and Glia: Cellular Mechanisms<br />- Synaptic Plasticity<br />-- Short-term plasticity |
| Session: |
563. Cannabinoids Poster |
| Presentation Time: | Monday, November 14, 2005 2:00 PM-3:00 PM |
| Location: | Washington Convention Center - Hall A-C, Board # UU80 |
| Keywords: | CANNABINOIDS, CEREBELLUM, TOLERANCE, ERK |
Chronic cannabinoid exposure results in tolerance to cannabinoid-induced locomotor effects which are mediated by the cannabinoid receptors (CB1R) located in motor control region, such as cerebellum. In cerebellar cortex, acute activation of presynaptic CB1R suppresses parallel fibers (PF) synaptic inputs to Purkinje cells (PC). Whole-cell patch-clamp recordings have been carried out in PC to analyze the properties of evoked excitatory synaptic transmission in mice chronically exposed to Δ9-THC or to its vehicle. Paired-pulse facilitation (PPF) was used to analyze PF-PC short-term synaptic plasticity. We observed a decreased PPF in mice chronically treated with THC, indicating an increased release probability after prolonged cannabinoid exposure. In addition, inhibition of PF-PC synaptic transmission induced by the selective CB1R agonist CP55940 is decreased in THC-treated mice. This suggests that, following chronic THC treatment, functional tolerance to the CB1R agonist occurs at cerebellar PF-PC synapses, likely due to a reduced efficacy of CB1R-mediated signalling. In order to explore the role of the Ras/ERK pathway in cannabinoid tolerance, we focused on a genetically engineered mouse model (RasGRF1 null mice), that does not develop behavioural tolerance after chronic treatment with Δ9-THC. The above reported alterations in short-term cerebellar synaptic plasticity and in CB1R-mediated signalling following chronic THC exposure are not evident in mice lacking RasGRF1 gene, indicating a role for the Ras/ERK pathway both in synaptic plasticity and in tolerance.
Our results indicate that chronic Δ9-THC exposure modulates cerebellar PF-PC synaptic activity. This might contribute to the behavioural tolerance to cannabinoid-induced locomotor effects observed following chronic cannabinoid administration.
Our results indicate that chronic Δ9-THC exposure modulates cerebellar PF-PC synaptic activity. This might contribute to the behavioural tolerance to cannabinoid-induced locomotor effects observed following chronic cannabinoid administration.
Supported by PRIN 2003 ( to R.Z.)
Sample Citation:
[Authors]. [Abstract Title]. Program No. XXX.XX. 2005 Neuroscience Meeting Planner. Washington, DC: Society for Neuroscience, 2005. Online.
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