Effects of prenatal alcohol and delta-9-tetrahydrocannabinol exposure via electronic cigarettes on motor development.

BACKGROUND: Prenatal alcohol exposure can lead to a wide range of neurological and behavioral deficits, including alterations in motor domains. However, much less is known about the effects of prenatal cannabis exposure on motor development, despite cannabis being the most consumed illicit drug among women. Cannabis use among pregnant women has become increasingly popular given the widespread perception that consumption is safe during pregnancy. Moreover, alcohol and cannabis are commonly used together, even among pregnant women. Yet few studies have explored the potential consequences of combined prenatal exposure on behavioral domains. METHODS: Using our previously established model, during gestational days 5 to 20, four groups of pregnant Sprague-Dawley rats were exposed to vaporized alcohol, delta-9-Tetrahydrocannabinol (THC) via electronic (e-) cigarettes, the combination of alcohol and THC, or a vehicle. Following birth, offspring were tested on early sensorimotor development, adolescent motor coordination, and adolescent activity levels. RESULTS: Prenatal THC e-cigarette exposure delayed sensorimotor development early in life and impaired motor coordination later in early adolescence; combined prenatal alcohol and THC exposure did not have additive effects on sensorimotor development. However, combined prenatal exposure produced hyperactivity among male offspring. CONCLUSIONS: Prenatal cannabis exposure may lead to impaired motor skills throughout early development and combined exposure with alcohol during gestation may lead to hyperactivity in early adolescence. These findings have important implications for informing pregnant women of the risks to the fetus associated with prenatal cannabis exposure, with and without alcohol, and could influence public policy.

Dietary supplementation with fish oil reverses high fat diet-induced enhanced sensitivity to the behavioral effects of quinpirole.

Consuming a high fat diet can lead to many negative health consequences, such as obesity, insulin resistance, and enhanced sensitivity to drugs acting on dopamine systems. It has recently been demonstrated that dietary supplementation with fish oil, which is rich in omega-3 fatty acids, can prevent this high fat diet-induced enhanced sensitivity to dopaminergic drugs from developing. However, it is not known whether fish oil supplementation can reverse this effect once it has already developed. To test the hypothesis that dietary supplementation with fish oil will reverse high fat diet-induced enhanced sensitivity to quinpirole, a dopamine D2/D3 receptor agonist, male Sprague-Dawley rats were fed either standard chow (17% kcal from fat), high fat chow (60% kcal from fat), standard chow, or high fat chow supplemented with 20% (w/w) fish oil. Body weight, food consumption, and sensitivity to quinpirole-induced (0.0032-0.32 mg/kg) penile erections were examined throughout the course of the experiment. Eating high fat chow enhanced sensitivity of rats to quinpirole-induced penile erections (i.e. resulted in a leftward shift of the ascending limb of the dose-response curve). Dietary supplementation with fish oil successfully treated this effect, as dose-response curves were not different for rats eating standard chow and rats eating high fat chow with fish oil. These results suggest that in addition to preventing the negative health consequences of eating a high fat diet, fish oil can also reverse some of these consequences once they have developed.

A Model of Combined Exposure to Nicotine and Tetrahydrocannabinol via Electronic Cigarettes in Pregnant Rats.

Nicotine and cannabis are two of the most commonly consumed licit and illicit drugs during pregnancy, often consumed together via e-cigarettes. Vaping is assumed to be a safer alternative than traditional routes of consumption, yet the potential consequences of prenatal e-cigarette exposure are largely unknown, particularly when these two drugs are co-consumed. In a novel co-exposure model, pregnant Sprague-Dawley rats received nicotine (36 mg/mL), tetrahydrocannabinol (THC) (100 mg/mL), the combination, or the vehicle via e-cigarettes daily from gestational days 5-20, mimicking the first and second human trimesters. Maternal blood samples were collected throughout pregnancy to measure drug and metabolite levels, and core body temperatures before and after exposure were also measured. Pregnant dams exposed to combined nicotine and THC had lower plasma nicotine and cotinine levels than those exposed to nicotine alone; similarly, the combined exposure group also had lower plasma THC and THC metabolite (THC-OH and THC-COOH) levels than those exposed to THC alone. Prenatal nicotine exposure gradually decreased initial core body temperatures each day, with chronic exposure, whereas exposure to THC decreased temperatures during the individual sessions. Despite these physiological effects, no changes were observed in food or water intake, weight gain, or basic litter outcomes. The use of this model can help elucidate the effects of co-exposure to THC and nicotine via e-cigarettes on both users and their offspring. Understanding the effects of co-use during pregnancy is critical for improving education for pregnant mothers about prenatal e-cigarette use and has important implications for public policy.

Haloperidol-induced hypokinesia in rats is differentially affected by the light/dark phase, age, and melatonin.

It has been well established that the striatal dopaminergic system is compromised with aging, namely D2 receptor function. Also well documented is the age related decline of the neurohormone, melatonin, in both humans and nonhuman animals. What has not been well studied is the possible interaction between the D2 receptor system and the age related decline in melatonin with its unmistakable pattern of synthesis and release exclusively during the dark phase. We tested the effect of the D2 antagonist, haloperidol (1.0 mg/kg ip), in adolescent (2 mo old) and adult rats (10 mo old) in the light (ZT3) and dark phases (ZT 15) in rats kept in a 12 L/12D cycle and the effect of exogenous melatonin (15 mg/kg ip/day x 4 days for a total of 60 mg/kg) on D2 antagonism. Using the bar test, measuring the extrapyramidal side-effect of hypokinesia, we report haloperidol to work differentially depending on both age and phase. Adult rats experienced the effect of the D2 antagonist in both the light and dark phases, while younger rats did not show hypokinetic affects in the dark. By manipulated lighting, we were able to restore the effect of haloperidol in younger rats in the dark phase. We also found ameliorating effects of melatonin lessening time on the bar after treatment with haloperidol, however, this effect was only found in older rats. These data demonstrate the importance of the light/dark cycle and age in the susceptibility of extrapyramidal effects with use of drugs that target D2 receptor function.