Abstract
Heavy cannabis consumption among adolescents is associated with significant and lasting neurobiological, psychological and health consequences that depend on the age of first use. Chronic exposure to cannabinoid agonists during the perinatal period or adolescence alters social behavior and prefrontal cortex (PFC) activity in adult rats. However, sex differences on social behavior as well as PFC synaptic plasticity after acute cannabinoid activation remain poorly explored. Here, we determined that the consequences of a single in vivo exposure to the synthetic cannabimimetic WIN55,212-2 differently affected PFC neuronal and synaptic functions after 24 h in male and female rats during the pubertal and adulthood periods. During puberty, single cannabinoid exposure (SCE) reduced play behavior in females but not males. In contrast, the same treatment impaired sociability in both sexes at adulthood. General exploration and memory recognition remained normal at both ages and both sexes. At the synaptic level, SCE ablated endocannabinoid-mediated synaptic plasticity in the PFC of females of both ages and heightened excitability of PFC pyramidal neurons at adulthood, while males were spared. In contrast, cannabinoid exposure was associated with impaired long-term potentiation (LTP) specifically in adult males. Together, these data indicate behavioral and synaptic sex differences in response to a single in vivo exposure to cannabinoid at puberty and adulthood.
Highlights
Cannabis is the most frequently and widely used illicit drug among adolescents in developed countries (Gowing et al, 2015)
Social behavior test: one subject removed from female WIN group for number of pouncing, number of pinning and number of total social interactions; open field test: one subject removed from Sham Male group for total distance traveled; novel object recognition test: one subject removed from Sham female group for index discrimination; patch-clamp experiments: three cells from two different rats removed from Sham female group, one cell removed from WIN female group and two cells from one rat removed from Sham male group for resting potential
We found that 24 h after a single in vivo exposure to a cannabinoid, the behavioral, neuronal and synaptic consequences differ depending on the sex and age of the rat
Summary
Cannabis is the most frequently and widely used illicit drug among adolescents in developed countries (Gowing et al, 2015). Chronic adolescent exposure to cannabinoids is linked to persistent adverse effects such as poor cognitive and psychiatric outcomes in adulthood (Levine et al, 2017) and regular cannabis use is associated with psychosocial impairment even in users without cannabis use disorder (Foster et al, 2017). The eCB system consists of CB1R and other eCB receptors (e.g., CB2R, TRPV1R), eCB, and the enzymatic machinery for eCB synthesis and degradation (Hu and Mackie, 2015). It participates in neuronal development and synaptic plasticity in most brain areas (Gaffuri et al, 2012; Manduca et al, 2012; Lu and Mackie, 2016)
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