The molecular logic of endocannabinoid signalling

Piomelli, Daniele

doi:10.1038/nrn1247

Cited by 1,757 publications

(1,754 citation statements)

References 144 publications

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“…These effects are observed at doses of AM404 that selectively target anandamide transport and produce only mild hypokinesia when the drug is administered alone (Beltramo et al, 2000). The results of this study, which have been confirmed in several subsequent reports (for review, see Piomelli, 2003), demarcate the pharmacological profile of AM404 from those of direct-acting cannabinoid drugs. This distinction may result from the ability of AM404 to enhance anandamide signaling in an activity-dependent manner, causing anandamide to accumulate in discrete regions of the brain and only when appropriate stimuli initiate its release.…”

Section: Behavioral Effects Of Anandamide Transport Inhibitorssupporting

confidence: 83%

“…However, additional routes of 2-AG synthesis also may exist, including phospholipase A 1 (PLA 1 ), hormone-sensitive lipase or a lipid phosphatase (Piomelli, 2003).…”

Section: -Arachidonoylglycerolmentioning

confidence: 99%

“…Basic research has shown that D 9 -tetrahydrocannabinol (D 9 -THC), the main active constituent of marijuana, produces its effects by combining with selective receptors present on the membrane of cells in the brain, the vasculature and the immune system (for review, see Piomelli, 2003). Research has also revealed that a group of lipid-derived substances produced by the body engages these receptors and participates in biological processes as diverse as pain perception, memory formation and blood pressure regulation (Piomelli, 2003). This knowledge has allowed researchers to interpret the pharmacological properties of marijuana, but remains inadequate to the task of developing strategies for the medicinal management of marijuana dependence.…”

Section: Introductionmentioning

confidence: 99%

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The endogenous cannabinoid system and the treatment of marijuana dependence

Piomelli

2004

Neuropharmacology

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Section: Behavioral Effects Of Anandamide Transport Inhibitorssupporting

confidence: 83%

“…However, additional routes of 2-AG synthesis also may exist, including phospholipase A 1 (PLA 1 ), hormone-sensitive lipase or a lipid phosphatase (Piomelli, 2003).…”

Section: -Arachidonoylglycerolmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The endogenous cannabinoid system and the treatment of marijuana dependence

Piomelli

2004

Neuropharmacology

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“…FAAH hydrolyzes the two most prominent endocannabinoids, N-arachidonoylethanolamine (anandamide, AEA) and 2-arachidonoylglycerol. These substances play manifold roles in both the central nervous system and in the periphery [10,11], reproductive organs included [12], mainly by activating G-protein coupled type-1 (CB 1 ) and type-2 (CB 2 ) cannabinoid receptors [13]. In the seminiferous tubules of the testis, both germ cells and somatic Sertoli cells possess a complete biochemical machinery to synthesize, transport, degrade and bind AEA and 2-arachidonoylglycerol [14][15][16].…”

Section: Introductionmentioning

confidence: 99%

The faah gene is the first direct target of estrogen in the testis: role of histone demethylase LSD1

Grimaldi

Pucci

Siena

et al. 2012

Cell. Mol. Life Sci.

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Estrogen (E 2 ) regulates spermatogenesis, yet its direct target genes have not been identified in the testis. Here, we cloned the proximal 5 0 flanking region of the mouse fatty acid amide hydrolase (faah) gene upstream of the luciferase reporter gene, and demonstrated its promoter activity and E 2 inducibility in primary mouse Sertoli cells. Specific mutations in the E 2 response elements (ERE) of the faah gene showed that two proximal ERE sequences (ERE2/3) are essential for E 2 -induced transcription, and chromatin immunoprecipitation experiments showed that E 2 induced estrogen receptor b binding at ERE2/3 sites in the faah promoter in vivo. Moreover, the histone demethylase LSD1 was found to be associated with ERE2/3 sites and to play a role in mediating E 2 induction of FAAH expression. E 2 induced epigenetic modifications at the faah proximal promoter compatible with transcriptional activation by remarkably decreasing methylation of both DNA at CpG site and histone H3 at lysine 9. Finally, FAAH silencing abolished E 2 protection against apoptosis induced by the FAAH substrate anandamide. Taken together, our results identify FAAH as the first direct target of E 2 .

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“…Cannabinoid receptors (CB1 and/or CB2) are present throughout the limbic forebrain, including the striatum and nucleus accumbens (Herkenham et al, 1991;Moldrich and Wenger, 2000;Fusco et al, 2004;Gong et al, 2006). Many functional effects of endocannabinoids in brain are thought to occur via CB1 receptors (Piomelli, 2003). CB1 receptors are located on GABAergic presynaptic axons in the nucleus accumbens shell (Matyas et al, 2006), and are often colocalized with m opioid receptors at the same synapses and in the same cells in striatum (Pickel et al, 2004;Schoffelmeer et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Endocannabinoid Hedonic Hotspot for Sensory Pleasure: Anandamide in Nucleus Accumbens Shell Enhances ‘Liking’ of a Sweet Reward

Mahler

Smith

Berridge

2007

Neuropsychopharmacol

306

259

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Cannabinoid drugs such as D 9 -THC are euphoric and rewarding, and also stimulate food intake in humans and animals. Little is known about how naturally occurring endogenous brain cannabinoids mediate pleasure from food or other natural sensory rewards. The taste reactivity paradigm measures effects of brain manipulations on affective orofacial reactions to intraorally administered pleasant and unpleasant tastes. Here we tested if anandamide microinjection into medial nucleus accumbens shell enhances these affective reactions to sweet and bitter tastes in rats. Anandamide doubled the number of positive 'liking' reactions elicited by intraoral sucrose, without altering negative 'disliking' reactions to bitter quinine. Anandamide microinjections produced Fos plumes of approximately 0.02-1 mm 3 volume. Plume-based maps, integrated with behavioral data, identified the medial shell of accumbens as the anatomical hotspot responsible for hedonic amplification. Anandamide produced especially intense hedonic enhancement in a roughly 1.6 mm 3 'hedonic hotspot' in dorsal medial shell, where anandamide also stimulated eating behavior. These results demonstrate that endocannabinoid signals within medial accumbens shell specifically amplify the positive hedonic impact of a natural reward (though identification of the receptor specificity of this effect will require future studies). Identification of an endocannabinoid hotspot for sensory pleasure gives insight into brain mechanisms of natural reward, and may be relevant to understanding the neural effects of cannabinoid drugs of abuse and therapeutic agents.

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The molecular logic of endocannabinoid signalling

Cited by 1,757 publications

References 144 publications

The endogenous cannabinoid system and the treatment of marijuana dependence

The endogenous cannabinoid system and the treatment of marijuana dependence

The faah gene is the first direct target of estrogen in the testis: role of histone demethylase LSD1

Endocannabinoid Hedonic Hotspot for Sensory Pleasure: Anandamide in Nucleus Accumbens Shell Enhances ‘Liking’ of a Sweet Reward

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