Effects of prenatal exposure to the CB-1 receptor agonist WIN 55212-2 or CO on the GABAergic neuronal systems of rat cerebellar cortex

Benagiano, Vincenzo; Lorusso, Loredana; Flace, Paolo; Girolamo, Francesco; Rizzi, Anna; Sabatini, R; Auteri, Peter; Bosco, L.; Cagiano, R.; Ambrosi, G

doi:10.1016/j.neuroscience.2007.07.050

Cited by 20 publications

(14 citation statements)

References 42 publications

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“…Offspring exposed to HU-210 in utero showed no significant difference from the non-exposed control group in average birth weight, body length, and lymphocyte immune function; however, 1μg/kg HU-210-exposed rats had a 17% increase in spleen size. WIN55,212-2 (0.5mg/kg s.c.) daily administration to rats during gestation had no effect on gestational progression, birthweight, or brain development into adulthood; however, glutamic acid decarboxylase (GAD-65/67) and γ-aminobutyric acid (GABA) expression in the cerebellar cortex was significantly higher than in controls (Benagiano et al, 2007). …”

Section: Resultsmentioning

confidence: 99%

Synthetic cannabinoids: Epidemiology, pharmacodynamics, and clinical implications

Castaneto¹,

Gorelick²,

Desrosiers³

et al. 2014

Drug and Alcohol Dependence

604

559

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Background Synthetic cannabinoids (SC) are a heterogeneous group of compounds developed to probe the endogenous cannabinoid system or as potential therapeutics. Clandestine laboratories subsequently utilized published data to develop SC variations marketed as abuseable “designer drugs.” In the early 2000’s, SC became popular as “legal highs” under brand names such as “Spice” and “K2,” in part due to their ability to escape detection by standard cannabinoid screening tests. The majority of SC detected in herbal products have greater binding affinity to the cannabinoid CB1 receptor than does Δ9-tetrahydrocannabinol (THC), the primary psychoactive compound in the cannabis plant, and greater affinity at the CB1 than the CB2 receptor. In-vitro and animal in-vivo studies show SC pharmacological effects 2-100 times more potent than THC, including analgesic, anti-seizure, weight-loss, anti-inflammatory, and anti-cancer growth effects. SC produce physiological and psychoactive effects similar to THC, but with greater intensity, resulting in medical and psychiatric emergencies. Human adverse effects include nausea and vomiting, shortness of breath or depressed breathing, hypertension, tachycardia, chest pain, muscle twitches, acute renal failure, anxiety, agitation, psychosis, suicidal ideation, and cognitive impairment. Long-term or residual effects are unknown. Due to these public health consequences, many SC are classified as controlled substances. However, frequent structural modification by clandestine laboratories results in a stream of novel SC that may not be legally controlled or detectable by routine laboratory tests. Methods We present here a comprehensive review, based on a systematic electronic literature search, of SC epidemiology and pharmacology and their clinical implications.

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Section: Resultsmentioning

confidence: 99%

Synthetic cannabinoids: Epidemiology, pharmacodynamics, and clinical implications

Castaneto¹,

Gorelick²,

Desrosiers³

et al. 2014

Drug and Alcohol Dependence

604

559

View full text Add to dashboard Cite

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“…Our results are in line with previous studies that showed significant decreases in total cerebellar GABA content following pre- and postnatal exposure to 150 or 300 ppm of CO [ 29 ]. More recently two studies by Benagiano et al, [ 22 , 23 ] also demonstrate that prenatal CO exposure (75 ppm) affects (decreases) quantitatively GAD and GABA immunoreactivity in the rat cerebellar cortex. These studies were made in the cerebellar cortex of the Vermis.…”

Section: Discussionmentioning

confidence: 95%

“…As reviewed by Benagiano et al, [ 22 , 23 ], numerous reports suggest that intrauterine and neonatal exposure to mild CO concentrations affects the course of CNS development. Studies have been done with chronic exposure of pregnant rats to CO at 75–150 ppm; concentrations below those associated with gross malformations or overt neurotoxic effects in the offspring [ 22 , 23 ]. However, mild CO exposure induced long-lasting consequences in the prenatal developing nervous system, and it is possibly implicated in the pathogenesis of persistent permanent neurological disorders detectable in adulthood [ 24 - 27 ].…”

Section: Introductionmentioning

confidence: 99%

“…For this reason the cerebellum is especially vulnerable to developmental irregularities [ 36 , 37 ]. Exposure to CO induces the formation of COHb and consequently a decrease of the tissue oxygen supply (hypoxia) [ 22 , 23 ]. The developing cerebellum is highly susceptible to prenatal CO exposure at low concentrations [ 28 , 29 ].…”

Section: Introductionmentioning

confidence: 99%

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Evidence for oxidative stress in the developing cerebellum of the rat after chronic mild carbon monoxide exposure (0.0025% in air)

et al. 2009

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Background: The present study was designed to test the hypothesis that chronic very mild prenatal carbon monoxide (CO) exposure (25 parts per million) subverts the normal development of the rat cerebellar cortex. Studies at this chronic low CO exposure over the earliest periods of mammalian development have not been performed to date. Pregnant rats were exposed chronically to CO from gestational day E5 to E20. In the postnatal period, rat pups were grouped as follows: Group A: prenatal exposure to CO only; group B: prenatal exposure to CO then exposed to CO from postnatal day 5 (P5) to P20; group C: postnatal exposure only, from P5 to P20, and group D, controls (air without CO). At P20, immunocytochemical analyses of oxidative stress markers, and structural and functional proteins were assessed in the cerebellar cortex of the four groups. Quantitative real time PCR assays were performed for inducible (iNOS), neuronal (nNOS), and endothelial (eNOS) nitric oxide synthases.

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“…Indeed, prenatal exposure to WIN 55,212-2, another CB 1 receptor agonist, is associated with long-lasting up-regulation of GABA immunoreactivity 81 , and increased GABA signaling due to receptor up-regulation has been shown to enhance motor performance 82 . It is important, however, to note that CB1 receptor levels rapidly increase during this exposure period in other brain areas related to motor function, including the basal ganglia, and cortex 53 .…”

Section: Discussionmentioning

confidence: 99%

Altered Motor Development Following Late Gestational Alcohol and Cannabinoid Exposure in Rats

Breit

Zamudio

Thomas

2019

Preprint

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Cannabis is the most commonly used illicit drug among pregnant women, and rates are likely to increase given recent legalization. In addition, half of pregnant women who report consuming cannabis also report drinking alcohol. However, little is known about the consequences of prenatal cannabis alone or combination with alcohol, particularly with cannabis products that are continually increasing in potency of the primary psychoactive constituent in cannabis, Δ9-tetrahydrocannabinol (THC). The current study investigated the effects of early exposure to cannabinoids during the brain growth spurt on early physical and motor development alone (Experiment 1) or in combination with alcohol (Experiment 2). In Experiment 1, Sprague-Dawley rat pups were exposed to a cannabinoid receptor agonist (CP-55,940 [CP]; 0.1, 0.25, 0.4 mg/kg/day), the drug vehicle, or a saline control from postnatal days (PD) 4-9. In Experiment 2, rat pups were exposed to CP (0.4 mg/kg/day) or the vehicle, and were additionally intubated with alcohol (11.9% v/v; 5.25 g/kg/day) or received a sham intubation. Subjects in both experiments were tested on a motor development task (PD 12-20) and a motor coordination task during adolescence (PD 30-32). Both developmental cannabinoid and alcohol exposure separately decreased body growth throughout development, and combined exposure exacerbated these effects, although only alcohol exposure induced long-term body weight reductions. Developmental cannabinoid exposure advanced early motor development, whereas alcohol exposure delayed development, and subjects given combined exposure did not differ from controls on some measures. Alcohol exposure impaired motor coordination later in life. In contrast, cannabinoid exposure, by itself did not significantly affect long-term motor coordination, but did exacerbate alcohol-related impairments in motor coordination among females. These results suggest that cannabinoid exposure may not only alter development by itself, but may exacerbate alcohol's teratogenic effects in specific 3 behavioral domains. These findings have important implications not only for individuals affected by prenatal exposure, but also for establishing public policy for women regarding cannabis use during pregnancy.

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Effects of prenatal exposure to the CB-1 receptor agonist WIN 55212-2 or CO on the GABAergic neuronal systems of rat cerebellar cortex

Cited by 20 publications

References 42 publications

Synthetic cannabinoids: Epidemiology, pharmacodynamics, and clinical implications

Synthetic cannabinoids: Epidemiology, pharmacodynamics, and clinical implications

Evidence for oxidative stress in the developing cerebellum of the rat after chronic mild carbon monoxide exposure (0.0025% in air)

Altered Motor Development Following Late Gestational Alcohol and Cannabinoid Exposure in Rats

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