Auditory gating in rat hippocampus and medial prefrontal cortex: Effect of the cannabinoid agonist WIN55,212-2

Dissanayake, Dilshani W. N.; Zachariou, Margarita; Marsden, C.A.; Mason, Robert J.

doi:10.1016/j.neuropharm.2008.08.039

Cited by 38 publications

(31 citation statements)

References 41 publications

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“…The cannabinoid agonists CP-55940 and WIN 55,212-2 have been shown to disrupt sensory gating in rats (141, 142). However, there are no studies that have examined the acute effects of cannabinoids on sensory gating (P50) in humans.…”

Section: Immediate Effects Of Cannabinoids: Experimental Evidencementioning

confidence: 99%

Gone to Pot â€“ A Review of the Association between Cannabis and Psychosis

2014

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Cannabis is the most commonly used illicit drug worldwide, with ~5 million daily users worldwide. Emerging evidence supports a number of associations between cannabis and psychosis/psychotic disorders, including schizophrenia. These associations-based on case-studies, surveys, epidemiological studies, and experimental studies indicate that cannabinoids can produce acute, transient effects; acute, persistent effects; and delayed, persistent effects that recapitulate the psychopathology and psychophysiology seen in schizophrenia. Acute exposure to both cannabis and synthetic cannabinoids (Spice/K2) can produce a full range of transient psychotomimetic symptoms, cognitive deficits, and psychophysiological abnormalities that bear a striking resemblance to symptoms of schizophrenia. In individuals with an established psychotic disorder, cannabinoids can exacerbate symptoms, trigger relapse, and have negative consequences on the course of the illness. Several factors appear to moderate these associations, including family history, genetic factors, history of childhood abuse, and the age at onset of cannabis use. Exposure to cannabinoids in adolescence confers a higher risk for psychosis outcomes in later life and the risk is dose-related. Individuals with polymorphisms of COMT and AKT1 genes may be at increased risk for psychotic disorders in association with cannabinoids, as are individuals with a family history of psychotic disorders or a history of childhood trauma. The relationship between cannabis and schizophrenia fulfills many but not all of the standard criteria for causality, including temporality, biological gradient, biological plausibility, experimental evidence, consistency, and coherence. At the present time, the evidence indicates that cannabis may be a component cause in the emergence of psychosis, and this warrants serious consideration from the point of view of public health policy.

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Section: Immediate Effects Of Cannabinoids: Experimental Evidencementioning

confidence: 99%

Gone to Pot â€“ A Review of the Association between Cannabis and Psychosis

2014

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“…WIN55,212-2 was purchased from Sigma/RBI, and SR141716A was a generous gift from the NIDA Drug Supply Program (Rockville, MD). Doses of WIN55,212-2 and SR141716A were chosen based on previous studies (Suzuki et al 2004;Kishimoto and Kano 2006;Dissanayake et al 2008).…”

Section: Conditioning Proceduresmentioning

confidence: 99%

Central cannabinoid receptors modulate acquisition of eyeblink conditioning

Steinmetz

Freeman²

2010

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Delay eyeblink conditioning is established by paired presentations of a conditioned stimulus (CS) such as a tone or light, and an unconditioned stimulus (US) that elicits the blink reflex. Conditioned stimulus information is projected from the basilar pontine nuclei to the cerebellar interpositus nucleus and cortex. The cerebellar cortex, particularly the molecular layer, contains a high density of cannabinoid receptors (CB1R). The CB1Rs are located on the axon terminals of parallel fibers, stellate cells, and basket cells where they inhibit neurotransmitter release. The present study examined the effects of a CB1R agonist WIN55,212-2 and antagonist SR141716A on the acquisition of delay eyeblink conditioning in rats. Rats were given subcutaneous administration of 1, 2, or 3 mg/kg of WIN55,212-2 or 1, 3, or 5 mg/kg of SR141716A before each day of acquisition training (10 sessions). Dose-dependent impairments in acquisition were found for WIN55,212-2 and SR141716A, with no effects on spontaneous or nonassociative blinking. However, the magnitude of impairment was greater for WIN55,212-2 than SR141716A. Dose-dependent impairments in conditioned blink response (CR) amplitude and timing were found with WIN55,212-2 but not with SR141716A. The findings support the hypothesis that CB1Rs in the cerebellar cortex play an important role in plasticity mechanisms underlying eyeblink conditioning.

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“…Preclinical studies had mixed results with CB1r antagonists sometimes alleviating schizophrenia-like positive symptoms [Martin et al , 2003, Tzavara et al , 2003, Madsen et al , 2006, Ferrer et al , 2007, Parolaro et al , 2010], although they were generally more effective at alleviating cannabinoid induced gating deficits [Mansbach et al , 1996, Martin et al , 2003, Dissanayake et al , 2008, Hajos et al , 2008, Parolaro et al , 2010]. Unfortunately, clinical trials failed to demonstrate beneficial effects of these drugs [Meltzer et al , 2004].…”

Section: Introductionmentioning

confidence: 99%

THC and endocannabinoids differentially regulate neuronal activity in the prefrontal cortex and hippocampus in the subchronic PCP model of schizophrenia

2015

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Cannabis use has been associated with an increased risk to develop schizophrenia as well as symptom exacerbation in patients. In contrast, clinical studies have revealed an inverse relationship between the CSF levels of the endocannabinoid anandamide and symptom severity, suggesting a therapeutic potential for endocannabinoid enhancing drugs. Indeed, preclinical studies have shown that these drugs can reverse distinct behavioral deficits in a rodent model of schizophrenia. The mechanisms underlying the differences between exogenous and endogenous cannabinoid administration are currently unknown. Using the phencyclidine (PCP) rat model of schizophrenia, we compared the effects on neuronal activity of systematic administration of delta-9-tetrahydrocannabinol (THC) with the fatty acid amide hydrolase inhibitor URB597. Specifically, we found that the inhibitory response in the prefrontal cortex to THC administration was absent in PCP-treated rats. In contrast, an augmented response to endocannabinoid upregulation was observed in the prefrontal cortex of PCP-treated rats. Interestingly, differential effects were also observed at the neuronal population level, as endocannabinoid upregulation induced opposite effects on coordinated activity when compared to THC. Such information is important for understanding why marijuana and synthetic cannabinoid use may be contraindicated in schizophrenia patients while endocannabinoid enhancement may provide a novel therapeutic approach.

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Auditory gating in rat hippocampus and medial prefrontal cortex: Effect of the cannabinoid agonist WIN55,212-2

Cited by 38 publications

References 41 publications

Gone to Pot â€“ A Review of the Association between Cannabis and Psychosis

Gone to Pot â€“ A Review of the Association between Cannabis and Psychosis

Central cannabinoid receptors modulate acquisition of eyeblink conditioning

THC and endocannabinoids differentially regulate neuronal activity in the prefrontal cortex and hippocampus in the subchronic PCP model of schizophrenia

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