Involvement of 5-hydroxytryptamine1A receptors in Δ9-tetrahydrocannabinol-induced catalepsy-like immobilization in mice

Egashira, Nobuaki; Matsuda, Tomomi; Koushi, Emi; Mishima, Kenichi; Iwasaki, Katsunori; Shoyama, Yukihiro; Fujiwara, Michihiro

doi:10.1016/j.ejphar.2006.08.051

Cited by 26 publications

(8 citation statements)

References 39 publications

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“…In CaMK- CB1 −/− mice, CB1 receptors are lost in all projecting neurons of the brain, thus making it difficult to define the exact site of action of THC to induce catalepsy. However, noradrenergic and serotonergic pathways (involving 5HT1a receptors) were proposed to play a role in THC-induced catalepsy [70,71]. Noradrenergic and serotonergic neurons likely express very low, but significant levels of CB1 [72,73].…”

Section: Discussionmentioning

confidence: 99%

Genetic Dissection of Behavioural and Autonomic Effects of Δ9-Tetrahydrocannabinol in Mice

et al. 2007

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Marijuana and its main psychotropic ingredient Δ9-tetrahydrocannabinol (THC) exert a plethora of psychoactive effects through the activation of the neuronal cannabinoid receptor type 1 (CB1), which is expressed by different neuronal subpopulations in the central nervous system. The exact neuroanatomical substrates underlying each effect of THC are, however, not known. We tested locomotor, hypothermic, analgesic, and cataleptic effects of THC in conditional knockout mouse lines, which lack the expression of CB1 in different neuronal subpopulations, including principal brain neurons, GABAergic neurons (those that release γ aminobutyric acid), cortical glutamatergic neurons, and neurons expressing the dopamine receptor D1, respectively. Surprisingly, mice lacking CB1 in GABAergic neurons responded to THC similarly as wild-type littermates did, whereas deletion of the receptor in all principal neurons abolished or strongly reduced the behavioural and autonomic responses to the drug. Moreover, locomotor and hypothermic effects of THC depend on cortical glutamatergic neurons, whereas the deletion of CB1 from the majority of striatal neurons and a subpopulation of cortical glutamatergic neurons blocked the cataleptic effect of the drug. These data show that several important pharmacological actions of THC do not depend on functional expression of CB1 on GABAergic interneurons, but on other neuronal populations, and pave the way to a refined interpretation of the pharmacological effects of cannabinoids on neuronal functions.

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Section: Discussionmentioning

confidence: 99%

Genetic Dissection of Behavioural and Autonomic Effects of Δ9-Tetrahydrocannabinol in Mice

et al. 2007

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“…The presence of an endocannabinoid system in the DRN may potentially explain certain behavioural effects elicited by cannabinoids, such as hypothermia, analgesia, impairment of memory, catalepsy and anxiety‐related responses, which have been all shown to be mediated by the 5‐HT system (Martin et al. , 1995; Malone and Taylor, 2001; Egashira et al. , 2002; 2006; Witkin et al.…”

Section: Discussionmentioning

confidence: 99%

Effect of the CB₁ receptor antagonists rimonabant and AM251 on the firing rate of dorsal raphe nucleus neurons in rat brain slices

Mendiguren¹,

Pineda²

2009

British J Pharmacology

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Background and purpose:Previous studies have suggested a regulation of 5-hydroxytryptamine (5-HT) neurons by the endocannabinoid system. The aim of our work was to examine the effect of two CB1 receptor antagonists, SR141716A (rimonabant, Sanofi-Synthélabo Recherche, Montpellier, France) and N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (AM251, Tocris Cookson, Bristol, UK), on the firing rate of dorsal raphe nucleus (DRN) neurons. Experimental approach: Single-unit extracellular recordings were performed to study the effect of CB1 receptor antagonists in slices of the DRN from rat brain. Key results: Rimonabant (1 mM) and AM251 (1 mM) decreased the firing rate of about 50% of all the recorded DRN 5-HT cells. The GABAA receptor antagonist picrotoxin (20 mM) (Sigma) prevented and also reversed the inhibitory effect of rimonabant (1 mM) and AM251 (1 mM), suggesting that CB1 receptors regulate 5-HT neurons through the GABAergic system. However, the CB1/CB2 receptor agonist R-(+)-[2,3-dihydro-5-methyl-3-[(morpholinyl)-methyl]pyrrolol[1,2,3-de]-1,4-benzoxazinyl]-(1-naphthalenyl) methanone mesylate salt (10 mM) (WIN55212-2, Sigma, St. Louis, MO, USA) failed to change the firing activity of non-5-HT (presumably GABAergic) neurons in the DRN. The endocannabinoid N-(2-hydroxyethyl)-5Z,8Z,11Z,14Z-eicosatetraenamide (anandamide, Tocris Cookson) (10 mM) also inhibited the firing activity of a number of 5-HT neurons, but this inhibition was not blocked by rimonabant (1 mM) or AM251 (1 mM), and the stable analogue R-(+) N-(2-hydroxy1methylethyl)-5Z,8Z,11Z,14Z-eicosatetraenamide (methanandamide, Tocris Cookson) (10 mM) did not mimic this effect. The selective CB1 receptor agonist arachidonoyl-2-chloroethylamide (ACEA) (1 mM) only slightly increased the firing rate of DRN 5-HT cells. Conclusions and implications:These results suggest a tonic/constitutive regulation of DRN 5-HT neurons by the endocannabinoid system, which may occur through a CB1 receptor-mediated inhibition of the GABAergic system. The inhibitory effect of anandamide may be mediated through a CB1 receptor-independent mechanism.

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“…Delta 9 -tetrahydrocannabinol (delta 9 -THC) is the most psychoactive component that was isolated in 1964 by Gaoni and Mechoulam at the Weizmann Institute in Rehovot (Israel). It has been demonstrated to produce hypothermia, learning and memory impairment, impairment of the prepulse inhibition of the startle reflex, catalepsy-like immobilisation, aggressive behaviour, analgesia, hypoactivity and enhancement of preference for high fat diet [1,2,3,4,5,6,84,85,86,87,88]. These effects are at least partly caused by binding to cannabinoid receptor type 1 (CB 1 ) within the brain.…”

Section: Introductionmentioning

confidence: 99%

Therapeutic Potential of Non-Psychotropic Cannabidiol in Ischemic Stroke

2010

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Cannabis contains the psychoactive component delta9-tetrahydrocannabinol (delta9-THC), and the non-psychoactive components cannabidiol (CBD), cannabinol, and cannabigerol. It is well-known that delta9-THC and other cannabinoid CB1 receptor agonists are neuroprotective during global and focal ischemic injury. Additionally, delta9-THC also mediates psychological effects through the activation of the CB1 receptor in the central nervous system. In addition to the CB1 receptor agonists, cannabis also contains therapeutically active components which are CB1 receptor independent. Of the CB1 receptor-independent cannabis, the most important is CBD. In the past five years, an increasing number of publications have focused on the discovery of the anti-inflammatory, anti-oxidant, and neuroprotective effects of CBD. In particular, CBD exerts positive pharmacological effects in ischemic stroke and other chronic diseases, including Parkinson’s disease, Alzheimer’s disease, and rheumatoid arthritis. The cerebroprotective action of CBD is CB1 receptor-independent, long-lasting, and has potent anti-oxidant activity. Importantly, CBD use does not lead to tolerance. In this review, we will discuss the therapeutic possibility of CBD as a cerebroprotective agent, highlighting recent pharmacological advances, novel mechanisms, and therapeutic time window of CBD in ischemic stroke.

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Involvement of 5-hydroxytryptamine1A receptors in Δ9-tetrahydrocannabinol-induced catalepsy-like immobilization in mice

Cited by 26 publications

References 39 publications

Genetic Dissection of Behavioural and Autonomic Effects of Δ9-Tetrahydrocannabinol in Mice

Genetic Dissection of Behavioural and Autonomic Effects of Δ9-Tetrahydrocannabinol in Mice

Effect of the CB₁ receptor antagonists rimonabant and AM251 on the firing rate of dorsal raphe nucleus neurons in rat brain slices

Therapeutic Potential of Non-Psychotropic Cannabidiol in Ischemic Stroke

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Involvement of 5-hydroxytryptamine1A receptors in Δ9-tetrahydrocannabinol-induced catalepsy-like immobilization in mice

Cited by 26 publications

References 39 publications

Genetic Dissection of Behavioural and Autonomic Effects of Δ9-Tetrahydrocannabinol in Mice

Genetic Dissection of Behavioural and Autonomic Effects of Δ9-Tetrahydrocannabinol in Mice

Effect of the CB1 receptor antagonists rimonabant and AM251 on the firing rate of dorsal raphe nucleus neurons in rat brain slices

Therapeutic Potential of Non-Psychotropic Cannabidiol in Ischemic Stroke

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Effect of the CB₁ receptor antagonists rimonabant and AM251 on the firing rate of dorsal raphe nucleus neurons in rat brain slices