Effects of cannabinoid drugs on the deficit of prepulse inhibition of startle in an animal model of schizophrenia: the SHR strain
Raquel Levin, Fernanda Fiel Peres, Valéria de Almeida, Mariana Bendlin Calzavara, Antônio Waldo Zuardi, Jaime E. C. Hallak, José Alexandre S. Crippa, Vanessa C. Abı́lio
Frontiers in Pharmacology 2014 DOI: 10.3389/fphar.2014.00010 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal experimental study Peer reviewed |
|---|---|
| Population | Spontaneously hypertensive rats (SHRs) and Wistar rats |
| Interventions | WIN55212 rimonabant AM404 cannabidiol |
| Topics | Cannabis CBD |
| Keywords | Prepulse inhibition Rimonabant Endocannabinoid system Pharmacology Schizophrenia object-oriented programming Startle response Antipsychotic Cannabinoid receptor antagonist Psychosis |
| Citations | 73 |
| Key findings | The cannabinoid agonist WIN55212 and cannabidiol reversed prepulse inhibition deficits in SHRs, while the CB1 antagonist rimonabant worsened them. |
Abstract
Clinical and neurobiological findings suggest that the cannabinoids and the endocannabinoid system may be implicated in the pathophysiology and treatment of schizophrenia. We described that the spontaneously hypertensive rats (SHR) strain presents a schizophrenia behavioral phenotype that is specifically attenuated by antipsychotic drugs, and potentiated by proschizophrenia manipulations. Based on these findings, we have suggested this strain as an animal model of schizophrenia. The aim of this study was to evaluate the effects of cannabinoid drugs on the deficit of prepulse inhibition (PPI) of startle, the main paradigm used to study sensorimotor gating impairment related to schizophrenia, presented by the SHR strain. The following drugs were used: (1) WIN55212,2 (cannabinoid agonist), (2) rimonabant (CB1 antagonist), (3) AM404 (anandamide uptake inhibitor), and (4) cannabidiol (CBD; indirect CB1/CB2 receptor antagonist, among other effects). Wistar rats (WRs) and SHRs were treated with vehicle (VEH) or different doses of WIN55212 (0.3, 1, or 3 mg/kg), rimonabant (0.75, 1.5, or 3 mg/kg), AM404 (1, 5, or 10 mg/kg), or CBD (15, 30, or 60 mg/kg). VEH-treated SHRs showed a decreased PPI when compared to WRs. This PPI deficit was reversed by 1 mg/kg WIN and 30 mg/kg CBD. Conversely, 0.75 mg/kg rimonabant decreased PPI in SHR strain, whereas AM404 did not modify it. Our results reinforce the role of the endocannabinoid system in the sensorimotor gating impairment related to schizophrenia, and point to cannabinoid drugs as potential therapeutic strategies.
Comparable studies
Other preclinical and animal studies on CBD, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Δ-9-Tetrahydrocannabinol and Cannabidiol produce dissociable effects on prefrontal cortical executive function and regulation of affective behaviors Rats | 2018 | Experimental study | |
| Optogenetic brain‐stimulation reward: A new procedure to re‐evaluate the rewarding versus aversive effects of cannabinoids in dopamine transporter‐Cre mice Transgenic dopamine transporter (DAT)-Cre mice | 2021 | Experimental study | |
| Effects of inhaled cannabis high in Δ9-THC or CBD on the aging brain: A translational MRI and behavioral study 19-20 month old mice | 2023 | Randomized controlled trial | |
| Cannabidiol tempers alcohol intake and neuroendocrine and behavioural correlates in alcohol binge drinking adolescent rats. Focus on calcitonin gene‐related peptide's brain levels Adolescent male rats | 2023 | Animal study | |
| Multi-level therapeutic actions of cannabidiol in ketamine-induced schizophrenia psychopathology in male rats. Male rats | 2024 | Experimental study |
Citations in the library
Cited by 8
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- Inverted U-Shaped Dose-Response Curve of the Anxiolytic Effect of Cannabidiol during Public Speaking in Real Life Frontiers in Pharmacology May 11, 2017
- Plastic and Neuroprotective Mechanisms Involved in the Therapeutic Effects of Cannabidiol in Psychiatric Disorders Frontiers in Pharmacology May 23, 2017
- Behavioral and Pharmacokinetic Profile of Indole-Derived Synthetic Cannabinoids JWH-073 and JWH-210 as Compared to the Phytocannabinoid Δ9-THC in Rats Frontiers in Neuroscience October 23, 2018
- Behavioral effects induced by the cannabidiol analogs HU-502 and HU-556. Behavioural Pharmacology June 1, 2023
and 3 more in the library
Cites 18
- Cannabidiol, a Cannabis sativa constituent, as an antipsychotic drug Brazilian Journal of Medical and Biological Research April 1, 2006
- Modulation of Mediotemporal and Ventrostriatal Function in Humans by Δ9-Tetrahydrocannabinol Archives of General Psychiatry April 1, 2009
- Psychological Effects of (S)-Ketamine and N,N-Dimethyltryptamine (DMT): A Double-Blind, Cross-Over Study in Healthy Volunteers Pharmacopsychiatry November 1, 2005
- New Perspectives in the Studies on Endocannabinoid and Cannabis: Cannabinoid Receptors and Schizophrenia Journal of Pharmacological Sciences 2004
- Potential antipsychotic properties of central cannabinoid (CB1) receptor antagonists The World Journal of Biological Psychiatry March 1, 2010
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