Effects on sleep and dopamine levels of microdialysis perfusion of cannabidiol into the lateral hypothalamus of rats

Murillo-Rodrı́guez, Eric; Palomero-Rivero, Marcela; Millán-Aldaco, Diana; Mechoulam, Raphael; Drucker-Colı́n, René

doi:10.1016/j.lfs.2011.01.013

Cited by 55 publications

(30 citation statements)

References 54 publications

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“…However, contradictory evidence on the effect of this cannabinoid on sleep exists, including both improvement (118) and diminution after systemic administration (584). Systemic administration to male rats during the light period enhances the total percentage of sleep (133), whereas enhancement of alertness is observed following injection into the lateral hypothalamus or dorsal raphe nuclei (612,613).…”

Section: Sleepmentioning

confidence: 99%

From Phytocannabinoids to Cannabinoid Receptors and Endocannabinoids: Pleiotropic Physiological and Pathological Roles Through Complex Pharmacology

Ligresti¹,

Petrocellis²,

Marzo³

2016

Physiological Reviews

378

337

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Apart from having been used and misused for at least four millennia for, among others, recreational and medicinal purposes, the cannabis plant and its most peculiar chemical components, the plant cannabinoids (phytocannabinoids), have the merit to have led humanity to discover one of the most intriguing and pleiotropic endogenous signaling systems, the endocannabinoid system (ECS). This review article aims to describe and critically discuss, in the most comprehensive possible manner, the multifaceted aspects of 1) the pharmacology and potential impact on mammalian physiology of all major phytocannabinoids, and not only of the most famous one ⌬ 9 -tetrahydrocannabinol, and 2) the adaptive prohomeostatic physiological, or maladaptive pathological, roles of the ECS in mammalian cells, tissues, and organs. In doing so, we have respected the chronological order of the milestones of the millennial route from medicinal/recreational cannabis to the ECS and beyond, as it is now clear that some of the early steps in this long path, which were originally neglected, are becoming important again. The emerging picture is rather complex, but still supports the belief that more important discoveries on human physiology, and new therapies, might come in the future from new knowledge in this field.

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Section: Sleepmentioning

confidence: 99%

From Phytocannabinoids to Cannabinoid Receptors and Endocannabinoids: Pleiotropic Physiological and Pathological Roles Through Complex Pharmacology

Ligresti¹,

Petrocellis²,

Marzo³

2016

Physiological Reviews

378

337

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“…CBD, and, in addition, increased cFos in the nucleus accumbens [115], an effect shared by typical and atypical antipsychotic drugs [116]. Intracerebroventricular administration of CBD (10 mg) also enhanced cFos expression in wakingrelated brain areas such as hypothalamus and dorsal raphe nucleus [117], but the relation between this finding and its antipsychotic properties is unclear.…”

Section: Cannabidiol and Psychosismentioning

confidence: 99%

“…A similar finding was found after Review. Cannabidiol and psychiatric disorders A. C. Campos et al 3371 microdialysis perfusion of CBD (30, 60 or 90 nM) into the rat lateral hypothalamus [117], a procedure that also enhanced alertness. It is unclear how this effect would relate to the antipsychotic properties of CBD because usual antipsychotic drugs act by antagonizing dopamine-2 receptors [123].…”

Section: Cannabidiol and Psychosismentioning

confidence: 99%

Multiple mechanisms involved in the large-spectrum therapeutic potential of cannabidiol in psychiatric disorders

Campos

Moreira

Gomes

et al. 2012

Phil. Trans. R. Soc. B

379

241

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Cannabidiol (CBD) is a major phytocannabinoid present in the Cannabis sativa plant. It lacks the psychotomimetic and other psychotropic effects that the main plant compound D 9 -tetrahydrocannabinol (THC) being able, on the contrary, to antagonize these effects. This property, together with its safety profile, was an initial stimulus for the investigation of CBD pharmacological properties. It is now clear that CBD has therapeutic potential over a wide range of non-psychiatric and psychiatric disorders such as anxiety, depression and psychosis. Although the pharmacological effects of CBD in different biological systems have been extensively investigated by in vitro studies, the mechanisms responsible for its therapeutic potential are still not clear. Here, we review recent in vivo studies indicating that these mechanisms are not unitary but rather depend on the behavioural response being measured. Acute anxiolytic and antidepressant-like effects seem to rely mainly on facilitation of 5-HT1A-mediated neurotransmission in key brain areas related to defensive responses, including the dorsal periaqueductal grey, bed nucleus of the stria terminalis and medial prefrontal cortex. Other effects, such as anti-compulsive, increased extinction and impaired reconsolidation of aversive memories, and facilitation of adult hippocampal neurogenesis could depend on potentiation of anandamidemediated neurotransmission. Finally, activation of TRPV1 channels may help us to explain the antipsychotic effect and the bell-shaped dose-response curves commonly observed with CBD. Considering its safety profile and wide range of therapeutic potential, however, further studies are needed to investigate the involvement of other possible mechanisms (e.g. inhibition of adenosine uptake, inverse agonism at CB2 receptor, CB1 receptor antagonism, GPR55 antagonism, PPARg receptors agonism, intracellular (Ca 2þ ) increase, etc.), on CBD behavioural effects.

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“…In accordance with its amnesic effects, it has been demonstrated that CBD infusions before training impairs long-term aversive memory acquisition (Resstel et al, 2006;Lemos et al, 2010); facilitation of aversive memory extinction before retrieval test (Bitencourt et al, 2008); and disruption of aversive memory reconsolidation immediately after retrieval test (Stern et al, 2012). Recently, it has been reported that CBD can modulate DA release and decrease the population activity of mesolimbic neurons (Ren et al, 2009;Murillo-Rodrı´guez et al, 2011. PFC dopaminergic neurotransmission is also essential for long-term storage of contextual fear memories (Espejo, 2003), which is supported by studies showing that reduced levels of DA release during contextual fear memory acquisition are associated with reduced freezing behavior (Pezze and Feldon, 2004;Ikegami et al, 2014).…”

Section: Discussionmentioning

confidence: 91%

“…CBD is known to act on multiple molecular targets and regulate dopaminergic and serotoninergic systems (MurilloRodrı´guez et al, 2011;Fogac¸a et al, 2014). In particular, it is known to regulate DA release in limbic structures and serotonin subtype 1A receptor (5-HT1 A )-mediated neurotransmission in PFC (Murillo-Rodrı´guez et al, 2011;Fogac¸a et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Selective post-training time window for memory consolidation interference of cannabidiol into the prefrontal cortex: Reduced dopaminergic modulation and immediate gene expression in limbic circuits

et al. 2017

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Abstract-The prefrontal cortex (PFC), amygdala and hippocampus display a coordinated activity during acquisition of associative fear memories. Evidence indicates that PFC engagement in aversive memory formation does not progress linearly as previously thought. Instead, it seems to be recruited at specific time windows after memory acquisition, which has implications for the treatment of posttraumatic stress disorders. Cannabidiol (CBD), the major non-psychotomimetic phytocannabinoid of the Cannabis sativa plant, is known to modulate contextual fear memory acquisition in rodents. However, it is still not clear how CBD interferes with PFC-dependent processes during post-training memory consolidation. Here, we tested whether intra-PFC infusions of CBD immediately after or 5 h following contextual fear conditioning was able to interfere with memory consolidation. Neurochemical and cellular correlates of the CBD treatment were evaluated by the quantification of extracellular levels of dopamine (DA), serotonin, and their metabolites in the PFC and by measuring the cellular expression of activity-dependent transcription factors in cortical and limbic regions. Our results indicate that bilateral intra-PFC CBD infusion impaired contextual fear memory consolidation when applied 5 h after conditioning, but had no effect when applied immediately after it. This effect was associated with a reduction in DA turnover in the PFC following retrieval 5 days after training. We also observed that post-conditioning infusion of CBD reduced c-fos and zif-268 protein expression in the hippocampus, PFC, and thalamus. Our findings support that CBD interferes with contextual fear memory consolidation by reducing PFC influence on cortico-limbic circuits. Ó

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Effects on sleep and dopamine levels of microdialysis perfusion of cannabidiol into the lateral hypothalamus of rats

Cited by 55 publications

References 54 publications

From Phytocannabinoids to Cannabinoid Receptors and Endocannabinoids: Pleiotropic Physiological and Pathological Roles Through Complex Pharmacology

From Phytocannabinoids to Cannabinoid Receptors and Endocannabinoids: Pleiotropic Physiological and Pathological Roles Through Complex Pharmacology

Multiple mechanisms involved in the large-spectrum therapeutic potential of cannabidiol in psychiatric disorders

Selective post-training time window for memory consolidation interference of cannabidiol into the prefrontal cortex: Reduced dopaminergic modulation and immediate gene expression in limbic circuits

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