Involvement of CB1 receptor in morphine withdrawal of adolescent mice prenatally treated with a cannabinoid agonist.

CANERO ELIANA M.; PEDRÓN VALERIA T.; VARANI ANDRÉS P.; AON, AMIRA J.; SORIANO DELIA B.; CALTANA LAURA R.; BRUSCO HERMINIA A.; BALERIO GRACIELA N.

Congreso; XLVIII REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE FARMACOLOGÍA EXPERIMENTAL. REUNIÓN CONJUNTA DE SOCIEDADES DE BIOCIENCIA.; 2016

There is evidence that prenatal exposure to cannabinoids agonists induce long-term alterations in the opioid system. In previous studies from our laboratory performed in adolescent CB1 KO mice prenatally treated with vehicle (VEH), we reported a decrease in the expression of naloxone (NAL) precipitated morphine (MOR) withdrawal syndrome compared to their wild-type (WT) littermates. In addition, WIN prenatal treatment induced an attenuation of MOR withdrawal syndrome in the WT, but not in the CB1 KO mice.The aim of the present study was to evaluate the effect of the prenatal exposure to the cannabinoid agonist, WIN, in c-Fos expression of certain brain areas of MOR withdrawn CB1 KO and WT adolescent mice.Pregnant female CB1 KO and WT mice received WIN (0.75 mg/kg, s.c.) or VEH once daily from 5th gestational day to parturition day. From the postnatal day 25 forward, mice were treated for 9 days with MOR (2 mg/kg, i.p.) or saline (SAL) twice daily. On the tenth day, the animals received NAL (6 mg/kg, i.p.) or SAL 60 min after the last injection in order to precipitate the withdrawal. Thirty minutes after NAL or SAL administration, mice were perfused with 4% paraformaldehyde solution. Brains were removed and coronal frozen sections were made at 30 μm on a freezing microtome to perform the c-Fos immunohistochemistry.WT but not KO adolescent mice prenatally treated with VEH showed a decrease in c-Fos expression during MOR withdrawal syndrome in Cg (p