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.