Effects of Cannabinoids on Neurotransmission

Szabó, Béla; Schlicker, Eberhard

doi:10.1007/3-540-26573-2_11

Cited by 195 publications

(138 citation statements)

References 161 publications

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“…The observed presynaptic inhibition is in line with the overwhelming evidence in the literature. Thus, to our knowledge, cannabinoids always inhibited synaptic transmission with a presynaptic mechanism (for review, see Szabo and Schlicker (2005)). The localization of CB 1 receptors is compatible with a presynaptic action, namely several classes of afferent inhibitory neurons of cortical pyramidal neurons express CB 1 receptors, and the CB 1 receptors appear at the axon terminals of these interneurons (Marsicano and Lutz, 1999;Bodor et al, 2005;Hill et al, 2007;Wedzony and Cochyk, 2009).…”

Section: Discussionmentioning

confidence: 99%

“…It is the primary neuronal target of the phytocannabinoid D 9 -tetrahydrocannabinol and endogenous cannabinoids (endocannabinoids) (Pertwee, 2005;Pertwee et al, 2010). Activation of CB 1 receptors leads to presynaptic inhibition of synaptic transmission in many regions of the central and peripheral nervous system (Freund et al, 2003;Szabo and Schlicker, 2005).…”

Section: Introductionmentioning

confidence: 99%

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Exogenous and Endogenous Cannabinoids Suppress Inhibitory Neurotransmission in the Human Neocortex

Kovacs

Knop

Urbanski

et al. 2011

Neuropsychopharmacol

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Activation of CB 1 receptors on axon terminals by exogenous cannabinoids (eg, D 9 -tetrahydrocannabinol) and by endogenous cannabinoids (endocannabinoids) released by postsynaptic neurons leads to presynaptic inhibition of neurotransmission. The aim of this study was to characterize the effect of cannabinoids on GABAergic synaptic transmission in the human neocortex. Brain slices were prepared from neocortical tissues surgically removed to eliminate epileptogenic foci. Spontaneous GABAergic inhibitory postsynaptic currents (sIPSCs) were recorded in putative pyramidal neurons using patch-clamp techniques. To enhance the activity of cannabinoidsensitive presynaptic axons, muscarinic receptors were continuously stimulated by carbachol. The synthetic cannabinoid receptor agonist WIN55212-2 decreased the cumulative amplitude of sIPSCs. The CB 1 antagonist rimonabant prevented this effect, verifying the involvement of CB 1 receptors. WIN55212-2 decreased the frequency of miniature IPSCs (mIPSCs) recorded in the presence of tetrodotoxin, but did not change their amplitude, indicating that the neurotransmission was inhibited presynaptically. Depolarization of postsynaptic pyramidal neurons induced a suppression of sIPSCs. As rimonabant prevented this suppression, it is very likely that it was due to endocannabinods acting on CB 1 receptors. This is the first demonstration that an exogenous cannabinoid inhibits synaptic transmission in the human neocortex and that endocannabinoids released by postsynaptic neurons suppress synaptic transmission in the human brain. Interferences of cannabinoid agonists and antagonists with synaptic transmission in the cortex may explain the cognitive and memory deficits elicited by these drugs.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Exogenous and Endogenous Cannabinoids Suppress Inhibitory Neurotransmission in the Human Neocortex

Kovacs

Knop

Urbanski

et al. 2011

Neuropsychopharmacol

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“…When given alone, rimonabant facilitated noradrenaline release, whereas SR 144528 had no effect. From Schlicker et al (1997) and Szabo and Schlicker (2005) . Tritium overflow corresponds to the release of noradrenaline, acetylcholine, dopamine, and serotonin.…”

Section: Effects On Transmitter Releasementioning

confidence: 99%

“…Although a rimonabant-sensitive effect of cannabinoids on GABA and glutamate release has been found in many studies [for a more complete review, see Szabo and Schlicker (2005)], rimonabant had an effect of its own in very few studies only. For example, in the paper by Slanina and Schweitzer (2005) in which cannabinoids had an inhibitory effect on glutamate release, rimonabant facilitated glutamate release in the absence of exogenously added cannabinoids, suggesting that the CB 1 receptor in this model is subject to an endogenous tone.…”

Section: Effects On Transmitter Releasementioning

confidence: 99%

Prejunctional and peripheral effects of the cannabinoid CB1 receptor inverse agonist rimonabant (SR 141716)

Diepen

Schlicker

Michel

2008

Naunyn-Schmied Arch Pharmacol

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Rimonabant is an inverse agonist specific for cannabinoid receptors and selective for their cannabinoid-1 (CB 1 ) subtype. Although CB 1 receptors are more abundant in the central nervous system, rimonabant has many effects in the periphery, most of which are related to prejunctional modulation of transmitter release from autonomic nerves. However, CB 1 receptors are also expressed in, e.g., adipocytes and endothelial cells. Rimonabant inhibits numerous cardiovascular cannabinoid effects, including the decrease of blood pressure by central and peripheral (cardiac and vascular) sites of action, with the latter often being endothelium dependent. Rimonabant may also antagonize cannabinoid effects in myocardial infarction and in hypotension associated with septic shock or liver cirrhosis. In the gastrointestinal tract, rimonabant counteracts the cannabinoid-induced inhibition of secretion and motility. Although not affecting most cannabinoid effects in the airways, rimonabant counteracts inhibition of smoothmuscle contraction by cannabinoids in urogenital tissues and may interfere with embryo attachment and outgrowth of blastocysts. It inhibits cannabinoid-induced decreases of intraocular pressure. Rimonabant can inhibit proliferation of, maturation of, and energy storage by adipocytes. Among the many cannabinoid effects on hormone secretion, only some are rimonabant sensitive. The effects of rimonabant on the immune system are not fully clear, and it may inhibit or stimulate proliferation in several types of cancer. We conclude that direct effects of rimonabant on adipocytes may contribute to its clinical role in treating obesity. Other peripheral effects, many of which occur prejunctionally, may also contribute to its overall clinical profile and lead to additional indications as well adverse events.

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“…The authors of the presented review distinguish several important mechanisms of action of cannabinoids, one of which is the ability to promote neuronal plasticity [31]. Additionally, by inhibiting calcium and potassium channels activation, cannabinoids are able to alter brain activity [32]. They are also involved in the control of glutamate-induced excitotoxicity [33].…”

Section: Introductionmentioning

confidence: 99%

Endocannabinoid system and cannabinoids in neurogenesis – new opportunities for neurological treatment? Reports from experimental studies.

Drab¹,

Haratym-Maj²,

Zagaja³

et al. 2017

J Pre Clin Clin Res.

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Neurogenesis is one of the most important phenomenona affecting human life. This process consists of proliferation, migration and differentiation of neuroblasts and synaptic integrations of newborn neurons. Proliferation of new cells continues into old age, also in humans, although the most extensive process of cell formation occurs during the prenatal period. It is possible to distinguish two regions in the brain responsible for neurogenesis: the dentate gyrus (DG) of the hippocampus and the sub-ventricular zone (SVZ). Hippocampal neurogenesis is very sensitive to various physiological and pathological stimuli. The functional integration of the newly-born dentate granule cells into hippocampal circuitry, and their ability to mediate long-term potentiation in DG, has led to the hypothesis that neurogenesis in the adult brain may play a key role in learning and memory function, as well as cognitive dysfunction in some diseases. Brain disorders, such as neurodegenerative diseases or traumatic brain injuries, significantly affect migration, proliferation and differentiation of neural cells. In searching for the best neurological drugs protecting neuronal cells, stimulating neurogenesis, while also developing no side-effects, endocannabinoids proved to be a strong group of substances having many beneficial properties. Therefore, the latest data is reviewed of the various experimental studies concerning the analysis of the most commonly studied cannabinoids and their impact on neurogenesis.

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Effects of Cannabinoids on Neurotransmission

Cited by 195 publications

References 161 publications

Exogenous and Endogenous Cannabinoids Suppress Inhibitory Neurotransmission in the Human Neocortex

Exogenous and Endogenous Cannabinoids Suppress Inhibitory Neurotransmission in the Human Neocortex

Prejunctional and peripheral effects of the cannabinoid CB1 receptor inverse agonist rimonabant (SR 141716)

Endocannabinoid system and cannabinoids in neurogenesis – new opportunities for neurological treatment? Reports from experimental studies.

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