Name: Preclinical Model of Prenatal Delta-9-Tetrahydrocannabinol Exposure to Assess Its Impact on Neurodevelopmental Outcomes (Video) | JoVE Journal
Uploaded: 2025-02-28T15:00:00.000+00:00
Duration: 5 min 13 s
Description: Learn a preclinical model for studying prenatal cannabinoid exposure using voluntary ingestion in rats. This method enables investigation of neurodevelopmental outcomes and informs public health guidelines.

ai_agent_IP

ai_agent

maintenance

instantTrialDurationMinutes

isBiopharma

enableNewMyJoveSectionDesign

educationFeatures

seoMetaApi

ai_copilot_institution_blacklist

ai_chat_institution_blacklist

freeAccessWindow

ssoRoleCapture

scheduledMaintenanceBanner

joveLabsFeatures

disable_autoplay_for_bots

extended_trial_duration

5 minutes

Thank you to the National Institute on Drug Abuse (NIDA) Drug Supply Program for the generous supply of THC. Supported by the University of New Mexico Department of Pediatrics Research Allocation Committee grant and the Division of Neonatology.

All procedures described here were approved by the University of New Mexico Health Sciences Center (UNM HSC) Institutional Animal Care and Use Committee (IACUC). All experiments were conducted in compliance with the ARRIVE guidelines. Long-Evans (Blue Spruce, HsdBlu: LE) rats were obtained from a commercial source. The males used were proven adult breeder rats, 12 weeks old upon arrival and 15-16 weeks old at the start of the breeding protocol. The females weighed 125-150 g and were approximately 6-7 weeks old upon arrival. At the time of breeding, the females were approximately 9-10 weeks old. It is critical to ensure that all prospective dams have no prior history of pregnancy. Allow at least one week for acclimation to the facility and their new housing environment. The first part of this protocol addresses pre-pregnancy cannabinoid consumption, while the second part focuses on pregnancy cannabinoid exposure. Details of the animals, reagents, and equipment used are provided in the Table of Materials. The experimental design is provided in Figure 1.
1. Pre-pregnancy cannabinoid exposure
<ol>
	<li>Housing and maintenance
	<ol>
		<li>House animals individually in standard rat static micro isolator cages with bedding at 22 &#176;C on a reverse 12-h light/dark schedule (lights on from 21:00 to 09:00 daily).</li>
		<li>Provide access to irradiated food (see Table of Materials) and tap water ad libitum throughout the study.</li>
	</ol>
	</li>
	<li>Material and chemical preparation
	<ol>
		<li>Obtain all required materials and chemicals (as provided in the Table of Materials).</li>
		<li>Keep research-grade THC in vials containing 10 mg/mL or 20 mg/mL THC dissolved in ethanol. 
		NOTE: Use appropriate personal protective equipment (PPE), as THC is a skin irritant and an aspiration hazard. Secure THC in a steel cabinet, as it is classified as a Schedule I controlled substance by the U.S. Department of Health and Human Services and the U.S. Food and Drug Administration.</li>
	</ol>
	</li>
	<li>Baseline measurements
	<ol>
		<li>Obtain baseline body weights for each female rat.</li>
	</ol>
	</li>
	<li>Preparation of THC-infused cookies
	<ol>
		<li>Prepare cookies 30 min prior to administration at 14:00 daily to maintain consistent feeding times.</li>
		<li>Separate mini chocolate cookies and add approximately half a teaspoon of peanut butter to the cream.</li>
		<li>Mix the required dose of THC (1.5 mg/kg for the first 2 days, followed by 3 mg/kg for 7 days) with the peanut butter before assembling the cookie.</li>
	</ol>
	</li>
	<li>Consumption evaluation
	<ol>
		<li>Provide a plain peanut butter/mini chocolate cookie for 2-4 days until consistent consumption is achieved. Remove water from the cage and administer the treat to each rat using forceps at 14:00 daily.</li>
		<li>Observe until the treat is completely consumed. Remove remnants if necessary. 
		NOTE: Administer THC at a dose of 1.5 mg/kg for 2 days, followed by 3 mg/kg for 7 days. Leave treats in the cage for up to 2 h for rats that do not consume immediately.</li>
		<li>Continue only with rats that show consistent treat consumption. Remove those with inconsistent ingestion from the experiment.</li>
		<li>Evaluate pre-pregnancy consumption for 2 weeks.</li>
	</ol>
	</li>
	<li>Post-PCE group assignment
	<ol>
		<li>Assign rats with consistent ingestion randomly to either the plain (control) or THC-infused (PCE) cookie group.</li>
		<li>Allow a minimum of 4 days without cookies prior to breeding to ensure THC clearance from their systems.</li>
	</ol>
	</li>
</ol>
2. Pregnancy (prenatal) cannabinoid exposure
<ol>
	<li>Breeding and pregnancy confirmation
	<ol>
		<li>Weigh the females to obtain a starting weight before placing them in a cage with a proven male breeder (male is THC-na&#239;ve).</li>
		<li>Ensure that the female rats do not consume a cookie during this time.</li>
		<li>Confirm pregnancy by the presence of a vaginal plug, which typically occurs 24 h after mating.</li>
		<li>Weigh the female rat and return it to the home cage. This is defined as Gestational Day (GD) 1.</li>
	</ol>
	</li>
	<li>THC infusion during pregnancy
	<ol>
		<li>Provide a plain or THC-infused (3 mg/kg) cookie at 14:00 daily starting at GD 1 for the duration of the pregnancy.</li>
		<li>Continue this regimen until the dam is noted to be nesting for delivery, at which point THC exposure is stopped.</li>
	</ol>
	</li>
	<li>Monitoring maternal weight gain
	<ol>
		<li>Weigh the rat dams twice a week to assess maternal weight gain. 
		NOTE: The new weights are also used to calculate how much THC to include in the cookie, adjusting the dose as necessary based on the dam&#39;s weight.</li>
	</ol>
	</li>
	<li>Cessation of THC exposure and birth documentation
	<ol>
		<li>Stop the THC exposure procedures when the dam is nesting around the expected time of delivery.</li>
		<li>Once offspring are born, record the number of live pups.</li>
		<li>Designate the day of birth as postnatal day (P) 0.</li>
	</ol>
	</li>
	<li>Weaning and housing of offspring
	<ol>
		<li>Wean the offspring at postnatal day (P) 23.</li>
		<li>Group house the weaned offspring with littermates based on sex.</li>
	</ol>
	</li>
	<li>Euthanasia of dams
	<ol>
		<li>Once the litter is weaned, euthanize the dams (when no longer needed) following institutionally approved protocols.</li>
	</ol>
	</li>
</ol>
3. Post-procedural steps
<ol>
	<li>Offspring housing and monitoring
	<ol>
		<li>Ensure all offspring are kept in appropriate housing conditions, ensuring proper temperature, light, and ventilation.</li>
		<li>Monitor pups regularly for any health or developmental issues, such as abnormal body weight or developmental delays (from postnatal day 1 onwards).</li>
	</ol>
	</li>
	<li>Baseline assessment
	<ol>
		<li>If required, assess baseline measures such as body weight, reflexes, or other relevant developmental parameters before initiating experiments on the offspring.</li>
	</ol>
	</li>
	<li>Experimental group assignment
	<ol>
		<li>Assign pups to experimental groups randomly to minimize any biases in testing.</li>
		<li>Limit the number of pups used per experiment to 1-2 pups from each litter to reduce potential litter effects.</li>
	</ol>
	</li>
</ol>

<ol><li>Volkow, N. D., Han, B., Compton, W. M., McCance-Katz, E. F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Self-reported+medical+and+nonmedical+cannabis+use+among+pregnant+women+in+the+United+States%5BTitle%5D)+AND+%22JAMA%22%5BJournal%5D)">Self-reported medical and nonmedical cannabis use among pregnant women in the United States.</a> JAMA. 322 (2), 167-169 (2019).</li>
<li>de Salas-Quiroga, A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Prenatal+exposure+to+cannabinoids+evokes+long-lasting+functional+alterations+by+targeting+CB1+receptors+on+developing+cortical+neurons%5BTitle%5D)+AND+%22Proc+Natl+Acad+Sci+USA%22%5BJournal%5D)">Prenatal exposure to cannabinoids evokes long-lasting functional alterations by targeting CB1 receptors on developing cortical neurons.</a> Proc Natl Acad Sci USA. 112 (44), 13693-13698 (2015).</li>
<li>Baglot, S. L., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Maternal-fetal+transmission+of+delta-9-tetrahydrocannabinol+%28THC%29+and+its+metabolites+following+inhalation+and+injection+exposure+during+pregnancy+in+rats%5BTitle%5D)+AND+%22J+Neurosci+Res%22%5BJournal%5D)">Maternal-fetal transmission of delta-9-tetrahydrocannabinol (THC) and its metabolites following inhalation and injection exposure during pregnancy in rats.</a> J Neurosci Res. 100 (3), 713-730 (2022).</li>
<li>Ryan, S. A., Ammerman, S. D., O'Connor, M. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Committee+on+Substance+Use+and+Prevention%3B+Section+on+Breastfeeding.+Marijuana+use+during+pregnancy+and+breastfeeding%3A+implications+for+neonatal+and+childhood+outcomes%5BTitle%5D)+AND+%22Pediatrics%22%5BJournal%5D)">Committee on Substance Use and Prevention; Section on Breastfeeding. Marijuana use during pregnancy and breastfeeding: implications for neonatal and childhood outcomes.</a> Pediatrics. 142 (3), e20181889(2018).</li>
<li>Corsi, D. J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Association+between+self-reported+prenatal+cannabis+use+and+maternal%2C+perinatal%2C+and+neonatal+outcomes%5BTitle%5D)+AND+%22JAMA%22%5BJournal%5D)">Association between self-reported prenatal cannabis use and maternal, perinatal, and neonatal outcomes.</a> JAMA. 322 (2), 145-152 (2019).</li>
<li>Duko, B., Dachew, B. A., Pereira, G., Alati, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((The+effect+of+prenatal+cannabis+exposure+on+offspring+preterm+birth%3A+a+cumulative+meta-analysis%5BTitle%5D)+AND+%22Addiction%22%5BJournal%5D)">The effect of prenatal cannabis exposure on offspring preterm birth: a cumulative meta-analysis.</a> Addiction. 118 (4), 607-619 (2023).</li>
<li>Scheyer, A. F., Melis, M., Trezza, V., Manzoni, O. J. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Trends+in+Neurosciences%5BTitle%5D)+AND+%22Trends+Neurosci%22%5BJournal%5D)">Trends in Neurosciences.</a> Trends Neurosci. 42 (12), 871-884 (2019).</li>
<li>Nashed, M. G., Hardy, D. B., Laviolette, S. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Prenatal+Cannabinoid+Exposure%3A+Emerging+Evidence+of+Physiological+and+Neuropsychiatric+Abnormalities%5BTitle%5D)+AND+%22Front+Psychiatry%22%5BJournal%5D)">Prenatal Cannabinoid Exposure: Emerging Evidence of Physiological and Neuropsychiatric Abnormalities.</a> Front Psychiatry. 11, 624275(2021).</li>
<li>Lin, A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Prenatal+cannabinoid+exposure%3A+why+expecting+individuals+should+take+a+pregnancy+pause+from+using+cannabinoid+products%5BTitle%5D)+AND+%22Front+Pediatr%22%5BJournal%5D)">Prenatal cannabinoid exposure: why expecting individuals should take a pregnancy pause from using cannabinoid products.</a> Front Pediatr. 11, 1278227(2023).</li>
<li>Chang, J. C., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Beliefs+and+attitudes+regarding+prenatal+marijuana+use%3A+perspectives+of+pregnant+women+who+report+use%5BTitle%5D)+AND+%22Drug+Alcohol+Depend%22%5BJournal%5D)">Beliefs and attitudes regarding prenatal marijuana use: perspectives of pregnant women who report use.</a> Drug Alcohol Depend. 196, 14-20 (2019).</li>
<li>Young-Wolff, K. C., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Trends+in+cannabis+polysubstance+use+during+early+pregnancy+among+patients+in+a+large+health+care+system+in+Northern+California%5BTitle%5D)+AND+%22JAMA+Netw+Open%22%5BJournal%5D)">Trends in cannabis polysubstance use during early pregnancy among patients in a large health care system in Northern California.</a> JAMA Netw Open. 5 (6), e2215418(2022).</li>
<li>Dickson, B., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Recommendations+from+cannabis+dispensaries+about+first-trimester+cannabis+use%5BTitle%5D)+AND+%22Obstet+Gynecol%22%5BJournal%5D)">Recommendations from cannabis dispensaries about first-trimester cannabis use.</a> Obstet Gynecol. 131 (6), 1031-1038 (2018).</li>
<li>Murphy, F., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Baby+boomers+and+cannabis+delivery+systems%5BTitle%5D)+AND+%22J+Drug+Issues%22%5BJournal%5D)">Baby boomers and cannabis delivery systems.</a> J Drug Issues. 45 (3), 293-313 (2015).</li>
<li>Barrus, D. G., et al. Tasty THC: Promises and challenges of cannabis edibles. <a target="_blank" href="http://scholar.google.com/scholar?hl=en&safe=off&q=author%3aBarrus%2C+DG+%22Methods+Rep%2C+RTI+Press%22">Methods Rep, RTI Press</a>. , 1-22 (2016).</li>
<li>Mura, P., Kintz, P., Dumestre, V., Raul, S., Hauet, T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((THC+can+be+detected+in+brain+while+absent+in+blood%5BTitle%5D)+AND+%22J+Anal+Toxicol%22%5BJournal%5D)">THC can be detected in brain while absent in blood.</a> J Anal Toxicol. 29 (8), 842-843 (2005).</li>
<li>Grotenhermen, F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Pharmacokinetics+and+pharmacodynamics+of+cannabinoids%5BTitle%5D)+AND+%22Clin+Pharmacol+Ther%22%5BJournal%5D)">Pharmacokinetics and pharmacodynamics of cannabinoids.</a> Clin Pharmacol Ther. 42 (4), 327-360 (2003).</li>
<li>Thompson, R., DeJong, K., Lo, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Marijuana+Use+in+Pregnancy%3A+A+Review%5BTitle%5D)+AND+%22Obstet+Gynecol+Surv%22%5BJournal%5D)">Marijuana Use in Pregnancy: A Review.</a> Obstet Gynecol Surv. 74 (7), 415-428 (2019).</li>
<li>Ravula, A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Pharmacokinetic+and+pharmacodynamic+characterization+of+tetrahydrocannabinol-induced+cannabinoid+dependence+after+chronic+passive+cannabis+smoke+exposure+in+rats%5BTitle%5D)+AND+%22Cannabis+Cannabinoid+Res%22%5BJournal%5D)">Pharmacokinetic and pharmacodynamic characterization of tetrahydrocannabinol-induced cannabinoid dependence after chronic passive cannabis smoke exposure in rats.</a> Cannabis Cannabinoid Res. 4 (4), 240-254 (2019).</li>
<li>Zgair, A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Dietary+fats+and+pharmaceutical+lipid+excipients+increase+systemic+exposure+to+orally+administered+cannabis+and+cannabis-based+medicines%5BTitle%5D)+AND+%22Am+J+Transl+Res%22%5BJournal%5D)">Dietary fats and pharmaceutical lipid excipients increase systemic exposure to orally administered cannabis and cannabis-based medicines.</a> Am J Transl Res. 8 (8), 3448-3459 (2016).</li>
<li>Mulligan, M. K., Hamre, K. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Influence+of+prenatal+cannabinoid+exposure+on+early+development+and+beyond%5BTitle%5D)+AND+%22Adv+Drug+Alcohol+Res%22%5BJournal%5D)">Influence of prenatal cannabinoid exposure on early development and beyond.</a> Adv Drug Alcohol Res. 3, 10981(2023).</li>
<li>Paul, S. E., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Associations+between+prenatal+cannabis+exposure+and+childhood+outcomes%3A+Results+from+the+ABCD+study%5BTitle%5D)+AND+%22JAMA+Psychiatry%22%5BJournal%5D)">Associations between prenatal cannabis exposure and childhood outcomes: Results from the ABCD study.</a> JAMA Psychiatry. 78 (1), 64-76 (2021).</li>
<li>Fügedi, G., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Increased+placental+expression+of+cannabinoid+receptor+1+in+preeclampsia%3A+An+observational+study%5BTitle%5D)+AND+%22BMC+Pregnancy+Childbirth%22%5BJournal%5D)">Increased placental expression of cannabinoid receptor 1 in preeclampsia: An observational study.</a> BMC Pregnancy Childbirth. 14, 395(2014).</li>
<li>Walker, M. K., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((A+less+stressful+alternative+to+oral+gavage+for+pharmacological+and+toxicological+studies+in+mice%5BTitle%5D)+AND+%22Toxicol+Appl+Pharmacol%22%5BJournal%5D)">A less stressful alternative to oral gavage for pharmacological and toxicological studies in mice.</a> Toxicol Appl Pharmacol. 260 (1), 65-69 (2012).</li>
<li>Brown, A. P., Dinger, N., Levine, B. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Stress+produced+by+gavage+administration+in+the+rat%5BTitle%5D)+AND+%22Contemp+Top+Lab+Anim+Sci%22%5BJournal%5D)">Stress produced by gavage administration in the rat.</a> Contemp Top Lab Anim Sci. 39 (1), 17-21 (2000).</li>
</ol>

The authors have no conflicts of interest to disclose.

The PCE paradigm outlined here involves voluntary THC consumption by pregnant rat dams. This is the first study to explore THC administration to pregnant rat dams via voluntary ingestion in a preclinical model. Both groups of rat dams consumed the same rat chow diet, minimizing potential variability in nutrition and caloric intake between groups. Animal models offer the advantage of controlling the timing and dosage of PCE for study purposes.
Pre-pregnancy consumption is assessed to identify r...

As rates of prenatal cannabinoid product use increase1, likely influenced by the growing legalization of cannabinoid products across the United States, studies are needed to better understand their impact on fetal development. Delta-9-tetrahydrocannabinol (THC), the psychoactive component of cannabinoid products, readily crosses the placenta and interacts with the endogenous endocannabinoid system2,3. The endogenous endocannabinoid system plays a critical role in neural development and may be a pathway through which developmental alterations occur. Cannabinoid use during pregnancy has been linked to reduced birth weight4 and an increased risk of premature birth5,6. Additional developmental abnormalities, such as deficits in social behavior and executive functions throughout life, have also been reported7,8,9.
Over time, changes in cannabinoid potency and patterns of use in the general population have highlighted the need for detailed studies on the potential effects of prenatal exposure on fetal development. The use of cannabinoid products during pregnancy is increasing, as these products are often perceived to alleviate symptoms such as depression, stress, pain, sleep disturbances, and nausea10,11. Dickson et al.12 conducted a study investigating recommendations from 400 cannabis dispensaries regarding first-trimester use in Colorado and found that approximately half of the dispensaries (50.5%) recommended edibles to pregnant individuals. It is often perceived that edibles avoid harm and health risks associated with smoking13,14, which results in many pregnant individuals consuming edibles.
Edibles deliver cannabinoids through the gastrointestinal system, where THC is absorbed into the bloodstream and transported via the portal vein to the liver for first-pass metabolism. In the liver, enzymes hydroxylate THC to produce 11-hydroxytetrahydrocannabinol (11-OH-THC), a highly potent psychoactive metabolite that easily crosses the blood-brain barrier15. Although it takes longer for the initial psychoactive effect of edibles (30-90 min), the resulting &#39;high&#39; lasts longer, with a peak at 2-4 h after ingestion16,17. The pharmacokinetic half-life of THC is 1.3-7.3 h in rats18,19.
Given the increasing utilization during pregnancy and the paucity of data on its impact on fetal neurodevelopment, a preclinical model of voluntary THC ingestion during pregnancy was developed, aligning more closely with the reported typical human use (oral consumption to alleviate nausea) to further describe the impact on neurodevelopmental outcomes.

<table><tbody><tr><td>5L0D PicoLab Laboratory Rodent Diet, irradiated</td><td>Purina LabDiet</td><td>5L0D</td><td></td></tr><tr><td>Cellulose/paper bedding BioFresh Comfort Bedding</td><td>BioFresh Vet</td><td>NA</td><td>https://biofreshvet.com/products/</td></tr><tr><td>Digital Kitchen Scale</td><td>Etekcity</td><td>EK4150</td><td></td></tr><tr><td>Female rats, 125-150 g&amp;nbsp;</td><td>Inotiv</td><td>14005F</td><td></td></tr><tr><td>Long-Evans rats (Blue Spruce, HsdBlu: LE)</td><td>Inotiv</td><td>14016M</td><td></td></tr><tr><td>N10 Rodent Plastic Cage Bottoms</td><td>Ancare</td><td>N10PLF</td><td></td></tr><tr><td>N10 Rodent Wire Lids</td><td>Ancare</td><td>N10SS</td><td></td></tr><tr><td>Narrow Pattern Forceps</td><td>Fine Science tools (FST)</td><td>11002-14</td><td></td></tr><tr><td>OREO mini chocolate Sandwich cookies, Go Paks, 12-3.5 oz cups</td><td>Amazon</td><td>B0198TUO7W</td><td></td></tr><tr><td>proven adult breeder males&amp;nbsp;</td><td>Inotiv</td><td>14016M</td><td></td></tr><tr><td>Rat static polysulfone microisolator cages (R20):</td><td></td><td></td><td></td></tr><tr><td>Research Grade THC&amp;nbsp; (only available with a DEA license, Schedule I drug)&amp;nbsp;</td><td>NIDA</td><td>NA</td><td>&amp;nbsp;https://nida.nih.gov/research/research-data-measures-resources/nida-drug-supply-program</td></tr><tr><td>SKIPPY Creamy Peanut Butter spread</td><td>Amazon</td><td>B0C75KZ28C</td><td></td></tr><tr><td>THC Consumption Supplies:</td><td></td><td></td><td></td></tr></tbody></table>

preclinical model of prenatal delta-9-tetrahydrocannabinol exposure to assess its impact on neurodevelopmental outcomes

Preclinical Model of Prenatal Delta-9-Tetrahydrocannabinol Exposure to Assess Its Impact on Neurodevelopmental Outcomes

Prenatal cannabinoid exposure (PCE) is becoming increasingly frequent as more states across the United States legalize recreational marijuana (cannabinoids). The consumption of cannabinoid products during pregnancy has been associated with various abnormal outcomes, although historical studies were conducted during a time when the potency of these products was approximately 300% lower than that of current products. Given the rising use of cannabinoids, it is essential to understand the potential impacts PCE may have on fetal neurodevelopment and subsequent infant and child development. Previous studies have demonstrated that PCE negatively affects learning and memory, behavioral skills, sleep, and attention in offspring. The aim of this study is to recapitulate PCE through voluntary ingestion of delta-9-tetrahydrocannabinol (THC), the psychoactive component of cannabinoid products, during pregnancy in a preclinical model. This article outlines the procedure for achieving moderate PCE throughout gestation. In this model, the control group consumes plain mini-chocolate/peanut butter cookies, while the PCE group consumes THC mixed into peanut butter paired with mini-chocolate cookies. This approach enables further investigation into the impact of PCE on developmental outcomes.

To establish voluntary consumption of THC, numerous treats were trialed to determine which ones were palatable to the rats and would be consumed quickly and consistently.
Initially, sugar-free strawberry-flavored gelatin cubes (1 cubic mL size), both with and without THC, were trialed. The amount of strawberry syrup flavoring was increased, and THC was trialed at three different concentrations (2 mg/kg/dose, 3 mg/kg/dose, and 5 mg/kg/dose). The rats did not consistently consume the cubes and w...

As legislative restrictions change, resulting in increased accessibility of cannabinoid products, it is critically important to develop models to study the impact of these exposures, particularly during pregnancy. A preclinical model of moderate prenatal cannabinoid exposure through voluntary ingestion has been developed, enabling more in-depth investigations.

Prenatal cannabinoid exposure (PCE) is becoming increasingly frequent as more states across the United States legalize recreational marijuana ...

preclinical-model-prenatal-delta-9-tetrahydrocannabinol-exposure-to

Research

JoVE Journal

Medicine

The NICU Network Neurobehavioral Scale (NNNS) was developed as an assessment for the at-risk infant. The purpose of this article is to describe the NNNS, provide video examples of the NNNS procedures and discuss the ways in which the exam has been used.

Assessment and Evaluation of the High Risk Neonate: The NICU Network Neurobehavioral Scale

The experimental designs proposed here focus on studying the effects of alcohol exposure in apoptosis and the application of neurotrophic peptide during pregnancy in fetal brain.  A detailed description from the breeding to the collection of fetal brains is described.  Techniques for determination of apoptosis are also described in detail.

Experimental Methods for Testing the Effects of Neurotrophic Peptide, ADNF-9, Against Alcohol-induced Apoptosis during Pregnancy in C57BL/6 Mice

We demonstrate the construction of alcohol vapor chambers using readily available materials that simultaneously house 6 mouse cages. We further describe their use in a mouse model of fetal alcohol exposure equivalent to all 3 trimesters of human pregnancy. This paradigm exposes animals during gestation and postnatal days 1-12.

Construction of Vapor Chambers Used to Expose Mice to Alcohol During the Equivalent of all Three Trimesters of Human Development

The goal of the protocol presented here is to describe procedures to expose rats to moderate levels of alcohol during prenatal brain development and to quantify resulting alterations in social behavior  during adulthood.

Moderate Prenatal Alcohol Exposure and Quantification of Social Behavior in Adult Rats

Encephalopathy of prematurity encompasses the central nervous system abnormalities associated with injury from preterm birth. This report describes a clinically relevant rat model of in utero transient systemic hypoxia-ischemia and intra-amniotic lipopolysaccharide administration (LPS) that mimics chorioamnionitis, and the related impact of infectious stimuli and placental underperfusion on CNS development.

Modeling Encephalopathy of Prematurity Using Prenatal Hypoxia-ischemia with Intra-amniotic Lipopolysaccharide in Rats

Anesthesia-induced developmental neurotoxicity (AIDN)  research has focused on rodents, which are not broadly applicable to humans. Non-human primate models are more relevant, but are cost-prohibitive and difficult to use for experimentation. The piglet, in contrast, is a clinically relevant, practical animal model ideal for the study of anesthetic neurotoxicity.

Use of a Piglet Model for the Study of Anesthetic-induced Developmental Neurotoxicity (AIDN): A Translational Neuroscience Approach

Exposure to environmental toxicants can acutely impact development with long-term effects. Detailed protocols are provided to illustrate a strategy using an effective lab model to study the effect of early embryonic exposure to bisphenol A. We provide fecundity and behavioral assays to monitor the effectiveness of our toxicant exposure bio-assays.

Long-term Behavioral and Reproductive Consequences of Embryonic Exposure to Low-dose Toxicants

The present protocol provides instructional information for using tobacco hornworm Manduca sexta in cannabinoid research. The method described here includes all necessary supplies and protocols to monitor physiological and behavioral changes of the insect model in response to cannabidiol (CBD) treatment.

Tobacco Hornworm as an Insect Model System for Cannabinoid Pre-clinical Studies

Cannabis distillate vape cartridges are battery-powered devices that aerosolize extracts containing high concentrations of cannabinoids. The absence of established preclinical models for these products creates challenges in studying their physiological effects. To address this gap, a standardized preclinical inhalation murine model for vaporized cannabis distillates has been developed.

Development of a Preclinical Inhalation Model to Test Vaporized Cannabis Distillates

Δ9-tetrahydrocannabinol (THC) is the intoxicating constituent in cannabis and a controlled substance in the United States. This article outlines standard procedures for obtaining, storing, and administering THC to mice complying with current legal regulations and briefly introduces a method to assess basic pharmacodynamic effects of THC in rodents.

Administration of &#916;9-Tetrahydrocannabinol (THC) in Adolescent and Adult Mice

Learn a preclinical model for studying prenatal cannabinoid exposure using voluntary ingestion in rats. This method enables investigation of neurodevelopmental outcomes and informs public health guidelines.

Preclinical Model of Prenatal Delta-9-Tetrahydrocannabinol Exposure to Assess Its Impact on Neurodevelopmental Outcomes

Explore More Videos