Persistent sexually dimorphic effects of adolescent THC exposure on hippocampal synaptic plasticity and episodic memory in rodents.
Aliza A Le, Julian Quintanilla, Mohammad Amani, Daniele Piomelli, Gary Lynch, Christine M Gall
Neurobiology of Disease January 2022 DOI: 10.1016/j.nbd.2021.105565 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental animal study Peer reviewed |
|---|---|
| Population | Adolescent rats and mice of both sexes, assessed in adulthood |
| Duration | 14-day course of daily treatments during adolescence, with assessments in adulthood |
| Topics | Cannabis Neuroplasticity |
| Keywords | Ca1 Cannabinoid Estrogen Frequency facilitation Lateral perforant path Long-term potentiation Sex differences Spatial learning Hippocampus |
| Key findings | A 14-day course of daily THC in adolescent rats and mice caused selective, sexually dimorphic deficits in hippocampal synaptic plasticity in adulthood. Females showed greater impairment, including disrupted endocannabinoid-dependent long-term potentiation in the lateral perforant path and, uniquely, in the Schaffer-commissural projection to CA1, with corresponding memory deficits. The authors argue these changes may underlie lasting cognitive effects of early-life cannabis use and may involve altered synaptic estrogen action. |
Abstract
There is evidence that cannabis use during adolescence leads to memory and cognitive problems in young adulthood but little is known about effects of early life cannabis exposure on synaptic operations that are critical for encoding and organizing information. We report here that a 14-day course of daily Δ9-tetrahydrocannabinol treatments administered to adolescent rats and mice (aTHC) leads to profound but selective deficits in synaptic plasticity in two axonal systems in female, and to lesser extent male, hippocampus as assessed in adulthood. Adolescent-THC exposure did not alter basic synaptic transmission (input/output curves) and had only modest effects on frequency facilitation. Nevertheless, aTHC severely impaired the endocannabinoid-dependent long-term potentiation in the lateral perforant path in females of both species, and in male mice; this was reliably associated with impaired acquisition of a component of episodic memory that depends on lateral perforant path function. Potentiation in the Schaffer-commissural (S-C) projection to field CA1 was disrupted by aTHC treatment in females only and this was associated with both a deficit in estrogen effects on S-C synaptic responses and impairments to CA1-dependent spatial (object location) memory. In all the results demonstrate sexually dimorphic and projection system-specific effects of aTHC exposure that could underlie discrete effects of early life cannabinoid usage on adult cognitive function. Moreover they suggest that some of the enduring, sexually dimorphic effects of cannabis use reflect changes in synaptic estrogen action.
Comparable studies
Other preclinical and animal studies on neuroplasticity, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psychedelics promote neuroplasticity through the activation of intracellular 5-HT2A receptors In vitro and in vivo (rodent) models | 2023 | Experimental study | |
| Psychedelics promote plasticity by directly binding to BDNF receptor TrkB Mice | 2023 | Experimental study | |
| Effects of psilocybin on hippocampal neurogenesis and extinction of trace fear conditioning Mice | 2013 | Experimental study | |
| The alkaloids of Banisteriopsis caapi, the plant source of the Amazonian hallucinogen Ayahuasca, stimulate adult neurogenesis in vitro Progenitor cells from subventricular and subgranular zones of adult mice brains | 2017 | In vitro experimental study | |
| N,N-dimethyltryptamine compound found in the hallucinogenic tea ayahuasca, regulates adult neurogenesis in vitro and in vivo Mice | 2020 | In vitro and in vivo experimental study |
Citations in the library
Cited by 4
- Adolescent THC impacts on mPFC dopamine-mediated cognitive processes in male and female rats. Psychopharmacology February 1, 2025
- Prior cannabis vapor exposure impairs pattern separation in rodents of multiple ages but is rescued by citicoline administration. Neuroscience May 25, 2026
- Adolescent female rats are resistant to the affective and cognitive impacts of Δ9-tetrahydrocannabinol exposure despite long-lasting molecular and neuronal disturbances in the hippocampal-hypothalamic network. Psychopharmacology November 1, 2025
- Astrocytic Ensemble at vHip-NAc synapses Modulates Cognitive Impairments Induced by Chronic THC Exposure
Cites 13
- Long-term consequences of adolescent cannabinoid exposure in adult psychopathology Frontiers in Neuroscience November 10, 2014
- Telling true from false: cannabis users show increased susceptibility to false memories Molecular Psychiatry March 31, 2015
- Cannabis and synaptic reprogramming of the developing brain. Nature Reviews Neuroscience July 2021
- Long-term hippocampal glutamate synapse and astrocyte dysfunctions underlying the altered phenotype induced by adolescent THC treatment in male rats. Pharmacological Research September 2016
- Sex and age specific effects of delta-9-tetrahydrocannabinol during the periadolescent period in the rat: The unique susceptibility of the prepubescent animal. Neurotoxicology and Teratology 2016
and 8 more in the library