Persistent sexually dimorphic effects of adolescent THC exposure on hippocampal synaptic plasticity and episodic memory in rodents

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 treat ment 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.