Δ<sup>9</sup>‐tetrahydrocannabinol increases endogenous extracellular glutamate levels in primary cultures of rat cerebral cortex neurons: Involvement of CB<sub>1</sub> receptors

Tomasini, Maria Cristina; Ferraro, Luca; Bebe, Berta Wonjie; Tanganelli, Sergio; Cassano, Tommaso; Cuomo, V.; Antonelli, Tiziana

doi:10.1002/jnr.10242

Cited by 25 publications

(13 citation statements)

References 23 publications

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“…This view is strengthened by the abundant perisomatic expression of CB 1 Rs in neocortical and PFC interneurons (Tsou et al, 1998;Marsicano and Lutz, 1999). Also, cannabinoids have been shown to increase cortical excitatory transmission and net spiking probability of pyramidal neurons in vivo (Pistis et al, 2001;Fortin et al, 2004), consistent with a concurrent increment of basal glutamate levels and decrement of basal GABA levels in prefrontocortical microdialysis experiments observed in anesthetized (Pistis et al, 2002) and awake (Ferraro et al, 2001) rats, as well as in prefrontocortical in vitro culture (Ferraro et al, 2001;Tomasini et al, 2002).…”

Section: Discussionmentioning

confidence: 66%

Cannabinoids Elicit Antidepressant-Like Behavior and Activate Serotonergic Neurons through the Medial Prefrontal Cortex

Bambico¹,

Katz²,

Debonnel³

et al. 2007

J. Neurosci.

293

213

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Preclinical and clinical studies show that cannabis modulates mood and possesses antidepressant-like properties, mediated by the agonistic activity of cannabinoids on central CB 1 receptors (CB 1 Rs). The action of CB 1 R agonists on the serotonin (5-HT) system, the major transmitter system involved in mood control and implicated in the mechanism of action of antidepressants, remains however poorly understood. In this study, we demonstrated that, at low doses, the CB 1 R agonist WIN55, 212-2 [R(ϩ)-[2,3-dihydro-5-methyl-3-[(morpholinyl)]pyrrolo[1,2,3-de]-1,4-benzoxazinyl]-(1-naphthalenyl) methanone mesylate] exerts potent antidepressant-like properties in the rat forced-swim test (FST). This effect is CB 1 R dependent because it was blocked by the CB 1 R antagonist rimonabant and is 5-HT mediated because it was abolished by pretreatment with the 5-HT-depleting agent parachlorophenylalanine. Then, using in vivo electrophysiology, we showed that low doses of WIN55,212-2 dose dependently enhanced dorsal raphe nucleus 5-HT neuronal activity through a CB 1 R-dependent mechanism. Conversely, high doses of WIN55,212-2 were ineffective in the FST and decreased 5-HT neuronal activity through a CB 1 R-independent mechanism. The CB 1 R agonist-induced enhancement of 5-HT neuronal activity was abolished by total or medial prefrontocortical, but not by lateral prefrontocortical, transection. Furthermore, 5-HT neuronal activity was enhanced by the local microinjection of WIN55,212-2 into the ventromedial prefrontal cortex (mPFCv) but not by the local microinjection of WIN55,212-2 into the lateral prefrontal cortex. Similarly, the microinjection of WIN55,212-2 into the mPFCv produced a CB 1 R-dependent antidepressantlike effect in the FST. These results demonstrate that CB 1 R agonists possess antidepressant-like properties and modulate 5-HT neuronal activity via the mPFCv.

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Section: Discussionmentioning

confidence: 66%

Cannabinoids Elicit Antidepressant-Like Behavior and Activate Serotonergic Neurons through the Medial Prefrontal Cortex

Bambico¹,

Katz²,

Debonnel³

et al. 2007

J. Neurosci.

293

213

View full text Add to dashboard Cite

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“…Rimonabant blocks the effects of THC in vitro (Rao et al 2004;Tomasini et al 2002), in animals (Compton et al 1996;Tseng and Craft 2004), and in humans . Furthermore, rimonabant has been shown in animals to modulate cannabinoid signaling in the reward circuitry in the brain (Le Foll and Goldberg 2005), thereby reducing opioid self-administration ), relapse to methamphetamine seeking (Anggadiredja et al 2004) or cocaine seeking (De Vries et al 2001), and alcohol self-administration (Arnone et al 1997;de Fonseca et al 2004).…”

Section: Introductionmentioning

confidence: 99%

Single and multiple doses of rimonabant antagonize acute effects of smoked cannabis in male cannabis users

et al. 2007

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Rationale-A single 90-mg dose of the cannabinoid CB1 receptor antagonist rimonabant attenuates effects of smoked cannabis in humans.Objectives-The objective of this study is to evaluate whether repeated daily 40-mg doses of rimonabant can attenuate effects of smoked cannabis to the same extent as a single higher (90 mg) dose.Materials and methods-Forty-two male volunteers received one of three oral drug regimens in a randomized, double blind, parallel group design: (1) 40 mg rimonabant daily for 15 days, (2) placebo for 14 days, then 90 mg rimonabant on day 15, or (3) placebo for 15 days. All participants smoked an active or placebo cannabis cigarette 2 h after medication on days 8 and 15. Subjective effects were measured with visual analog scales and the marijuana-scale of the Addiction Research Center Inventory.Results-Cannabis-induced tachycardia was significantly lower for the 40-mg group on day 8 and for the 40 and 90 mg rimonabant groups on day 15 as compared to placebo. The 40-mg dose significantly decreased peak subjective effects on day 8. Neither the 90-mg nor 40-mg doses significantly decreased peak subjective effects on day 15. Rimonabant treatment did not significantly affect Δ 9 -tetrahydrocannabinnol pharmacokinetics.Conclusions-Repeated lower daily rimonabant doses (40 mg) attenuated the acute physiological effects of smoked cannabis to a similar degree as a single 90-mg dose; repeated 40-mg doses attenuated subjective effects after 8 but not 15 days.

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“…In addition, as both cannabinoids (Shen and Thayer 1999;Pistis et al 2002;Tomasini et al 2002) and HIV (Ferrarese et al 2001;Chang et al 2002) have been shown to affect the glutamatergic system, we also expected to observe interactive effects between HIV and chronic marijuana use on brain glutamate concentrations.…”

Section: Introductionmentioning

confidence: 99%

Combined and Independent Effects of Chronic Marijuana Use and HIV on Brain Metabolites

Chang

Cloak

Yakupov

et al. 2006

Jrnl NeuroImmune Pharm

106

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The effects of chronic marijuana (MJ) use on brain function remain controversial. Because MJ is often used by human immunodeficiency virus (HIV) patients, the aim of this study was to evaluate whether chronic MJ use and HIV infection are associated with interactive or additive effects on brain chemistry and cognitive function. We evaluated 96 subjects (30 seronegative nondrug users, 24 MJ users, 21 HIV without MJ use, 21 HIV + MJ) using proton magnetic resonance spectroscopy and a battery of neuropsychological tests. The two primarily abstinent MJ user groups showed no significant differences on calculated estimates of lifetime grams of delta9-tetrahydrocannabinol exposure, despite some differences in usage pattern. The two HIV groups also had similar HIV disease severity (CD4 cell count, plasma viral load, HIV dementia staging, Karnofsky score). On two-way analyses of covariance, HIV infection (independent of MJ) was associated with trends for reduced N-acetyl aspartate (NA) in the parietal white matter and increased choline compounds (CHO) in the basal ganglia. In contrast, MJ (independent of HIV) was associated with decreased basal ganglia NA (−5.5%, p = 0.05), CHO (−10.6%, p = 0.04), and glutamate (−9.5%, p = 0.05), with increased thalamic creatine (+6.1%, p = 0.05). HIV + MJ was associated with normalization of the reduced glutamate in frontal white matter (interaction p = 0.01). After correction for age, education, or mood differences, MJ users had no significant abnormalities on neuropsychological test performance, and HIV subjects only had slower reaction times. These findings suggest chronic MJ use may lead to decreased neuronal and glial metabolites, but may normalize the decreased glutamate in HIV patients.

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Δ⁹‐tetrahydrocannabinol increases endogenous extracellular glutamate levels in primary cultures of rat cerebral cortex neurons: Involvement of CB₁ receptors

Cited by 25 publications

References 23 publications

Cannabinoids Elicit Antidepressant-Like Behavior and Activate Serotonergic Neurons through the Medial Prefrontal Cortex

Cannabinoids Elicit Antidepressant-Like Behavior and Activate Serotonergic Neurons through the Medial Prefrontal Cortex

Single and multiple doses of rimonabant antagonize acute effects of smoked cannabis in male cannabis users

Combined and Independent Effects of Chronic Marijuana Use and HIV on Brain Metabolites

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Δ9‐tetrahydrocannabinol increases endogenous extracellular glutamate levels in primary cultures of rat cerebral cortex neurons: Involvement of CB1 receptors

Cited by 25 publications

References 23 publications

Cannabinoids Elicit Antidepressant-Like Behavior and Activate Serotonergic Neurons through the Medial Prefrontal Cortex

Cannabinoids Elicit Antidepressant-Like Behavior and Activate Serotonergic Neurons through the Medial Prefrontal Cortex

Single and multiple doses of rimonabant antagonize acute effects of smoked cannabis in male cannabis users

Combined and Independent Effects of Chronic Marijuana Use and HIV on Brain Metabolites

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Product

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Δ⁹‐tetrahydrocannabinol increases endogenous extracellular glutamate levels in primary cultures of rat cerebral cortex neurons: Involvement of CB₁ receptors