QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, November 12, 2003, 23(32):10311-10320

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (26) Citing Articles via Google Scholar Google Scholar Articles by Huang, Y.-C. Articles by Gean, P.-W. Search for Related Content PubMed PubMed Citation Articles by Huang, Y.-C. Articles by Gean, P.-W.

 Previous Article  |  Next Article 

Development/Plasticity/Repair
Mediation of Amphetamine-Induced Long-Term Depression of Synaptic Transmission by CB₁ Cannabinoid Receptors in the Rat Amygdala

Ya-Chun Huang,^1,2 Su-Jane Wang,³ Lih-Chu Chiou,⁴ and Po-Wu Gean²

¹Institute of Basic Medical Sciences and ²Department of Pharmacology, National Cheng-Kung University, Tainan, Taiwan 701, ³School of Medicine, Fu Jen Catholic University, Taipei, Taiwan 242, and ⁴Department of Pharmacology, National Taiwan University, Taipei, Taiwan 100

The amygdala is thought to mediate memory consolidation of amphetamine-induced conditioned place preference, a behavioral paradigm that requires memory for an association between environmental cues and the affective state produced by the drug treatment. Here we show that amphetamine induces long-term synaptic depression (LTD) in the amygdala. Amphetamine LTD is not affected by dopamine, serotonin 1A, and norepinephrine 2 receptor antagonists but is blocked by the cannabinoid CB₁ receptor antagonist AM251. It is mimicked by the CB₁ agonist WIN55212-2 and facilitated and partially occluded by endocannabinoid uptake inhibitor AM404. Both amphetamine and WIN55212-2 LTDs are associated with an increase in the ratio of paired-pulse facilitation and a decrease in the frequency but not the amplitude of miniature EPSCs. They are also sensitive to block by P/Q type calcium channel blocker and occluded by each other, indicating that these two forms of synaptic plasticity share a common underlying mechanism. Loading postsynaptic neuron with calcium chelator blocked amphetamine LTD in some but not all neurons tested. However, in the presence of AM404, amphetamine LTD was present in all neurons recorded. These results suggest that amphetamine-induced endocannabinoid release depends on a rise in intracellular calcium and the incomplete block of LTD in some neurons may be attributable to the spillover of endocannabinoid from nearby cells. The finding that endocannabinoids underlie the synaptic actions of amphetamine may open a new avenue for the treatment of psychostimulants addiction.

Key words: amphetamine; endocannabinoid; amygdala; LTD; synaptic plasticity; addiction

---

Received May 28, 2003; revised August 13, 2003; accepted September 10, 2003.

This article has been cited by other articles:

				B. Pan, C. J. Hillard, and Q.-s. Liu Endocannabinoid Signaling Mediates Cocaine-Induced Inhibitory Synaptic Plasticity in Midbrain Dopamine Neurons J. Neurosci., February 6, 2008; 28(6): 1385 - 1397. [Abstract] [Full Text] [PDF]

				P. Pacher, S. Batkai, and G. Kunos The Endocannabinoid System as an Emerging Target of Pharmacotherapy Pharmacol. Rev., September 1, 2006; 58(3): 389 - 462. [Abstract] [Full Text] [PDF]

				V. A. Bender, K. J. Bender, D. J. Brasier, and D. E. Feldman Two coincidence detectors for spike timing-dependent plasticity in somatosensory cortex. J. Neurosci., April 19, 2006; 26(16): 4166 - 4177. [Abstract] [Full Text] [PDF]

				M. H. Milekic, S. D. Brown, C. Castellini, and C. M. Alberini Persistent disruption of an established morphine conditioned place preference. J. Neurosci., March 15, 2006; 26(11): 3010 - 3020. [Abstract] [Full Text] [PDF]

				P. J. Zhu and D. M. Lovinger Retrograde Endocannabinoid Signaling in a Postsynaptic Neuron/Synaptic Bouton Preparation from Basolateral Amygdala J. Neurosci., June 29, 2005; 25(26): 6199 - 6207. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help