Sex differences in the behavioral and synaptic consequences of a single exposure to cannabinoid at puberty and adulthood

Abstract

2Heavy cannabis consumption among adolescents is associated with significant and lasting 2 3 neurobiological, psychological and health consequences that depend on the age of first use. 4Chronic exposure to cannabinoid (CB) agonists during adolescence alters social behavior and 2 5 prefrontal cortex (PFC) activity in adult rats. However, sex differences on social behavior as 2 6well as PFC synaptic plasticity after acute CB activation remain poorly explored. Here, we 2 7 determined the consequences of a single CB activation differently affects PFC in males and 2 8 females by assessing social behavior and PFC neuronal and synaptic functions in rats during 2 9 pubertal or adulthood periods, 24h after a single in-vivo cannabinoid exposure (SCE). During 3 0 puberty, SCE reduced play behavior in females but not males. In contrast, SCE impaired 3 1 sociability in both sexes at adulthood. General exploration and memory recognition remained 3 2 normal at both ages and both sexes. At the synaptic level, SCE ablated endocannabinoid-3 3 mediated long-term depression (eCB-LTD) in the PFC of females of both ages and 3 4 heightened excitability of PFC pyramidal neurons at adulthood, while males were spared. In 3 5 contrast, SCE was associated to impaired long-term potentiation in adult males. Together, the 3 6 data indicate behavioral and synaptic sex differences in response to a single in-vivo exposure 3 7to cannabinoid at puberty and adulthood. 3 8 3 9