Cannabidiol Reverses MK-801-Induced Disruption of Prepulse Inhibition in Mice

Long, Leonora E.; Malone, Daniel Thomas; Taylor, David A.

doi:10.1038/sj.npp.1300838

Cited by 156 publications

(130 citation statements)

References 57 publications

Supporting

Mentioning

104

Contrasting

Unclassified

Order By: Relevance

“…Strengthening these results, CBD reversed the disruption of prepulse inhibition (PPI) of the startle response in mice caused by MK-801, a glutamate receptor antagonist, as did clozapine, further supporting the idea that this compound may act as an atypical antipsychotic drug. 62 Consistent with the behavioral data, both CBD and clozapine, but not haloperidol, induced Fos immunoreactivity (Fos) in the prefrontal cortex, while only haloperidol increased Fos in the dorsal striatum. 63,64 Even in human models of psychotic symptoms induced in healthy volunteers, the antipsychotic-like activity of CBD can be demonstrated.…”

Section: Antipsychotic Actionsupporting

confidence: 70%

Cannabidiol: from an inactive cannabinoid to a drug with wide spectrum of action

Zuardi

2008

Rev. Bras. Psiquiatr.

356

302

View full text Add to dashboard Cite

Section: Antipsychotic Actionsupporting

confidence: 70%

Cannabidiol: from an inactive cannabinoid to a drug with wide spectrum of action

Zuardi

2008

Rev. Bras. Psiquiatr.

356

302

View full text Add to dashboard Cite

“…That study found that neither haloperidol nor clozapine reversed the effects of MK-801 on PPI. However clozapine has been reported by others to attenuate the effects of MK-801 on PPI in mice (Lipina et al 2005;Long et al 2006) but those studies did not test effects of a typical antipsychotic.…”

Section: Discussionmentioning

confidence: 99%

Typical and atypical antipsychotic drug effects on locomotor hyperactivity and deficits in sensorimotor gating in a genetic model of NMDA receptor hypofunction

Duncan

Moy

Lieberman

et al. 2006

Pharmacology Biochemistry and Behavior

View full text Add to dashboard Cite

Psychotomimetic effects of NMDA antagonists in humans suggest that NMDA receptor hypofunction could contribute to the pathophysiology of schizophrenia. A mouse line that expresses low levels of the NMDA R1 subunit (NR1) of the NMDA receptor was generated to model endogenous NMDA hypofunction. These mutant mice show increased locomotor activity, increased acoustic startle reactivity and deficits in prepulse inhibition (PPI) of acoustic startle. The present study examined effects of a typical antipsychotic drug, haloperidol, and two atypical antipsychotic drugs (olanzapine and risperidone) on behavioral alterations in the NR1 hypomorphic (NR1 −/−) mice. Haloperidol significantly reduced activity in the wild type controls at each dose tested (.05, 0.1, and 0.2 mg/kg). The NR1 −/− mice were less sensitive to the haloperidol-induced locomotor inhibition in comparison to the NR1 +/+ mice. In contrast to haloperidol, olanzapine reduced the hyperactivity in the NR1 −/− mice at a dose that produced minimal effects on locomotor activity in the wild type mice. These data suggest that non-dopaminergic blocking properties of olanzapine contribute to the drug's ability to reduce hyperactivity in the NR1 deficient mice. In the PPI paradigm, haloperidol (0.5 mg/kg) did not affect the increased startle reactivity in the NR1 −/− mice, but did reduce startle amplitude in the NR1 +/+ mice. Haloperidol increased PPI in both the mutant and wild type strains. Unlike haloperidol, risperidone (0.3 mg/kg) and olanzapine (3 mg/kg) reduced startle magnitude in both NR1 +/+ and NR1 −/− mice. Like haloperidol, risperidone and olanzapine increased PPI in both NR1 +/+ and NR1 −/− mice. The similar effects of these atypical antipsychotic drugs in wild type mice and mice with markedly reduced NR1 expression suggest that the drugs were not working by a NMDA receptor-dependent mechanism to increase PPI. Since both haloperidol and the atypical drugs increased PPI, it is likely that D 2 dopamine receptor blockade is responsible for the drug effects on sensorimotor gating.

show abstract

“…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]. Moreover, studies with animal models that involve dopaminergic stimulation suggest that the antipsychotic-like doses of CBD (60-120 mg kg 21 ) are higher than those needed to induce anxiolytic-like effects [7,91,92] and reverse behavioural deficits induced by the NMDA receptor antagonist MK-801 [93,94,99]. These findings indicate that the mechanisms of CBD effects on glutamateor dopamine-based models could be at least partially distinct.…”

Section: Cannabidiol and Psychosismentioning

confidence: 99%

“…This mechanism, probably by facilitating the pre-synaptic release of glutamate [80], is involved in the ability of CBD to reverse the disruption of PPI induced by the NMDA receptor antagonist MK-801 [93].…”

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

377

241

View full text Add to dashboard Cite

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.

show abstract

Cannabidiol Reverses MK-801-Induced Disruption of Prepulse Inhibition in Mice

Cited by 156 publications

References 57 publications

Cannabidiol: from an inactive cannabinoid to a drug with wide spectrum of action

Cannabidiol: from an inactive cannabinoid to a drug with wide spectrum of action

Typical and atypical antipsychotic drug effects on locomotor hyperactivity and deficits in sensorimotor gating in a genetic model of NMDA receptor hypofunction

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

Contact Info

Product

Resources

About