title: Mediation of amphetamine-induced long-term depression of synaptic transmission by CB1 cannabinoid receptors in the rat amygdala.
abstract: 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 alpha2 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.
authors: Institute of Basic Medical Sciences, National Cheng-Kung University, Tainan, Taiwan.
authors: Ya-Chun
authors: YC
authors: Huang
authors: Su-Jane
authors: SJ
authors: Wang
authors: Lih-Chu
authors: LC
authors: Chiou
authors: Po-Wu
authors: PW
authors: Gean
mesh_terms: D000661:Amphetamine / Q000494:pharmacology*; D000679:Amygdala / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology; D048588:Benzoxazines; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D008024:Ligands; D036881:Long-Term Synaptic Depression / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009025:Morpholines / Q000494:pharmacology; D009281:Naphthalenes / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D010880:Piperidines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
chemical_list: D001095:Arachidonic Acids; D048588:Benzoxazines; D015220:Calcium Channels; D000697:Central Nervous System Stimulants; D018492:Dopamine Antagonists; D008024:Ligands; D009025:Morpholines; D009281:Naphthalenes; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; C103505:AM 251; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; D000661:Amphetamine; D002118:Calcium; C107594:N-(4-hydroxyphenyl)arachidonylamide