Cannabinoids can cross the placenta, thus may interfere with fetal endocannabinoid signaling during neurodevelopment, causing long-lasting deficits. Despite increasing reports of cannabis consumption during pregnancy, the protracted consequences of prenatal cannabinoid exposure (PCE) remain incompletely understood. Here, we report sex-specific differences in behavioral and neuronal deficits in the adult progeny of rat dams exposed to low doses of cannabinoids during gestation. In males, PCE reduced social interaction, ablated endocannabinoid long-term depression (LTD) and heightened excitability of prefrontal cortex pyramidal neurons, while females were spared. Group 1 mGluR and endocannabinoid signaling regulate emotional behavior and synaptic plasticity. Notably, sex-differences following PCE included levels of mGluR1/5 and TRPV1R mRNA. Finally, positive allosteric modulation of mGlu5 and enhancement of anandamide levels restored LTD and social interaction in PCE adult males. Together, these results highlight marked sexual differences in the effects of PCE and introduce strategies for reversing detrimental effects of PCE.

Rosmarinic acid is commonly found in species of the Boraginaceae and the subfamily Nepetoideae (Lamiaceae). It has a number of interesting biological activities, for example, antiviral, antibacterial, anti-inflammatory, and antioxidant. The aim of the present study was to investigate the effect of the i.p. administration of caffeic and rosmarinic acid (5 and 10 mg/kg) on anti-inflammatory and nociceptive response using carrageenan-induced pleurisy model and tail-flick assay in rats. The analysis of cells in the pleural exudates revealed a reduction of 66% of the number of leukocytes that migrated to the pleural cavity in the animals treated with 5 mg/kg caffeic acid, and of 92.9% for the animals treated with 10 mg/kg in comparison with the control group. These exudates showed a balanced distribution of polymorphonuclear (PMN) and mononuclear (MN) cells, differently from the control group, in which PMN cells were predominant. The analysis to tail-flick latency was increased in the group treated with 10 mg/kg caffeic acid characterizing a nociceptive response. While there was no difference between control group and animals treated with rosmarinic.