B CB1 receptors and preterm birth Corticosterone and prenatal stress

Cannabinoid CBa receptor blockade with rimonabant (SR141716) administered during late pregnancy in mice resulted in a modest (less than 1 day in mice) but highly significant shortening of pregnancy. Similarly, CB1 receptor knockout mice displayed a shorter gestational period than wildtype mice. Analogous silencing of the CB2 receptor did not affect gestational length (Wang et al., 2008). Interestingly, a slight but significant reduction on gestational length was reported in a population of heavy (>6 times a week) marijuana smoking women (Fried et al., 1984).

The study by Dey and colleagues (Wang et al., 2008) also reported a shift in peak levels of corticosterone (CCS) to an earlier gestational age in CB1 receptor knockout mice (from day 17-18 in wild type to day 15-16 CB1 in knockouts). Strikingly, a similar shift of the maternal CCS peak values was observed in prenatally stressed rats (day 17 compared to day 18 of gestation in controls) (Fride and Weinstock, 1985; Weinstock et al., 1988). These observations support our earlier contention that the sequelae of prenatal manipulation of the ECS, such as seen after marijuana consumption during pregnancy, overlap with the consequences of prenatal stress (Fride and Mechoulam, 1996). Therefore, we speculate that the impairments in emotional regulation and cognitive performance induced by prenatal exposure to stress (Fride and Weinstock, 1988; Fride et al, 1985, 1986, 2004), which have also been observed as a consequence of pre- and perinatal cannabinoid exposure (Campolongo et al., 2007; Mereu et al., 2003; Newsom and Kelly, 2008; Trezza et al., 2008), may be explained by maternal stress-induced changes in fetal ECS development (Fride and Mechoulam, 1996). Indeed, recently, we have shown that "ultramild" prenatal stress (Meek et al., 2000) results in an alteration of the ''prepulse inhibition (PPI) of the startle reflex'' (Fig. 6.1A), a behavioral assay for sensorimotor gating, used as an assessment of adaptability and schizophrenia-like symptoms (Crawley, 2000; Varty et al., 2001). Thus, we observed that the PPI in prenatally stressed mice was not adversely affected; rather a more robust PPI response was observed than in controls. Similarly, a lack of adverse effects on the PPI response was reported both in mice which were exposed to repeated postnatal stress

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