Adolescent exposure to delta-9-tetrahydrocannabinol and ethanol heightens sensitivity to fear stimuli.
Cora E Smiley, Heyam K Saleh, Katherine E Nimchuk, Constanza Garcia-Keller, Justin T Gass
Behavioural Brain Research October 11, 2021 DOI: 10.1016/j.bbr.2021.113517 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical animal study Peer reviewed |
|---|---|
| Population | Rodents (animal models) |
| Interventions | Delta-9-tetrahydrocannabinol (THC) Ethanol N-acetylcysteine (NAC) |
| Topics | PTSD Cannabis |
| Keywords | Adolescence Cannabis abuse Glutamate N-acetylcysteine Prelimbic cortex |
| Key points | Adolescent exposure to THC and ethanol in rodents produced enhanced behavioral and neuronal sensitivity to fear stimuli, and these effects were attenuated by the glutamatergic modulator N-acetylcysteine. The authors propose that adolescent THC and ethanol exposure alters fear processing through glutamate-dependent modifications in prelimbic cortex signaling. |
Abstract
Cannabis use disorder (CUD) has doubled in prevalence over the past decade as a nation-wide trend toward legalization allows for increased drug accessibility. As a result, marijuana has become the most commonly used illicit drug in the United States particularly among the adolescent population. This is especially concerning since there is greater risk for the harmful side effects of drug use during this developmental period due to ongoing brain maturation. Increasing evidence indicates that CUD often occurs along with other debilitating conditions including both alcohol use disorder (AUD) and anxiety disorders such post-traumatic stress disorder (PTSD). Additionally, exposure to cannabis, alcohol, and stress can induce alterations in glutamate regulation and homeostasis in the prefrontal cortex (PFC) that may lead to impairments in neuronal functioning and cognition. Therefore, in order to study the relationship between drug exposure and the development of PTSD, these studies utilized rodent models to determine the impact of adolescent exposure to delta-9-tetrahydrocannabinol (THC) and ethanol on responses to fear stimuli during fear conditioning and used calcium imaging to measure glutamate activity in the prelimbic cortex during this behavioral paradigm. The results from these experiments indicate that adolescent exposure to THC and ethanol leads to enhanced sensitivity to fear stimuli both behaviorally and neuronally. Additionally, these effects were attenuated when animals were treated with the glutamatergic modulator N-acetylcysteine (NAC). In summary, these studies support the hypothesis that adolescent exposure to THC and ethanol leads to alterations in fear stimuli processing through glutamatergic reliant modifications in PFC signaling.
Comparable studies
Other preclinical and animal studies on cannabis, most cited first.
Citations in the library
Cites 13
- Cannabis, a cause for anxiety? A critical appraisal of the anxiogenic and anxiolytic properties Journal of Translational Medicine October 2, 2020
- Effects of ∆9-tetrahydrocannabinol on aversive memories and anxiety: a review from human studies. BMC Psychiatry August 26, 2020
- Adolescent exposure to Δ9-tetrahydrocannabinol alters the transcriptional trajectory and dendritic architecture of prefrontal pyramidal neurons. Molecular Psychiatry April 2019
- Concomitant THC and stress adolescent exposure induces impaired fear extinction and related neurobiological changes in adulthood. Neuropharmacology January 2019
- A Model of Δ9-Tetrahydrocannabinol Self-administration and Reinstatement That Alters Synaptic Plasticity in Nucleus Accumbens. Biological Psychiatry October 15, 2018
and 8 more in the library