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 January 1, 2014 DOI: 10.3389/fphar.2014.00010 via OpenAlex
Summary
Cannabinoid drugs affect sensorimotor gating deficits in spontaneously hypertensive rats (SHRs), a strain used as an animal model of schizophrenia. SHRs showed reduced prepulse inhibition (PPI) compared to Wistar rats, indicating impaired sensorimotor gating. The cannabinoid agonist WIN55212 (1 mg/kg) and cannabidiol (30 mg/kg) reversed this PPI deficit, while the CB1 antagonist rimonabant (0.75 mg/kg) worsened it. The anandamide uptake inhibitor AM404 had no effect. These findings suggest cannabinoid drugs may offer therapeutic strategies for schizophrenia-related sensorimotor gating impairments.
Study at a glance
| Characteristics | Animal experimental study Peer reviewed |
|---|---|
| Population | Spontaneously hypertensive rats (SHRs) and Wistar rats |
| Interventions | WIN55212 rimonabant AM404 cannabidiol |
| Topics | Cannabis |
| Keywords | Prepulse inhibition Rimonabant Endocannabinoid system Pharmacology |
| Citations | 73 |
| Key finding | 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.