L 368 899 hydrochloride

OXT (Sigma-Aldrich, St Louis, MO, USA) and L-368,899 hydrochloride (Tocris Bioscience, Abingdon, UK), an OXT receptor antagonist, were dissolved in saline and subcutaneously injected into the mice. L-368,899 (10 mg/kg) was injected into pregnant WT female mice at GD19. The average length of time between injection and delivery was 6.9 h ± 26 min (n = 31). In the prenatal treatments, OXT (83 IU [0.2–0.26 mg]/kg) was injected into pregnant WT female mice 5 min before C/S (preOXT-C/S). In postnatal treatments, OXT (31.3 mIU/pup) was injected 30 min after delivery into naturally delivered or C/S-delivered pups as well as pups born to L-368,899-treated or OXT-KO dams (ND-OXT, C/S-OXT, LND-OXT, or IVF-OKO-OXT, respectively). The treatment doses of L-368,899 and OXT were determined based on previous reports^{27 (link)}. Saline vehicle was injected into all mice 30 min after delivery for the non-treated animals (ND, C/S, LND, IVF-WT, or IVF-OKO).

Synthetic human oxytocin (Cell Sciences, CRO300GB) was dissolved in sterile water and administered at doses of 1 or 3 mg/kg (1 ml/kg, i.p.) 30 min prior to testing. This pretreatment interval and dose range were based on prior literature showing an effective reduction in drug seeking with minimal side effects [17 (link), 56 (link), 57 (link)]. The oxytocin receptor antagonist L-368,899 hydrochloride (Tocris, 2641) was dissolved in sterile water and administered at a dose of 5 mg/kg (1 ml/kg, i.p.) 30 min prior to testing, which has been shown to effectively block the effects of oxytocin in rats [58 (link)]. The dual orexin receptor antagonist DORA-12 (Merck) was dissolved in 5% DMSO + 40% captisol in sterile water and administered at doses of 10 mg/kg (1 ml/kg, i.p.) or 30 mg/kg (3 ml/kg, i.p.) based on effective doses of other DORAs reported in the literature [47 (link)–50 (link)]. Heroin (diamorphine hydrochloride) was dissolved in 0.9% saline (0.04 mg/50 μl infusion per reward). Dustless precision grain-based food pellets (45 mg each, Bio-Serv, F0165) were delivered in 3-pellet quantities per reward.