Table 1.

Summary of studies utilizing E11-18 dosing schedule.

Study Name	Morphine Dose/Exposure Time	Pup treatment?	Age at testing?	Main effects?	Interventions?	Citation for E11-18?
Ahmadalipour and Rashidy-Pour (2015)	E11-18 2x daily. First 3 injections 5 mg/kg, remaining injections 10 mg/kg. SubQ.	Cross-fostered so each mother raised half-saline and half morphine-exposed pups. Litters reduced to 10 maximum. Sexes of pups not tested; sex not considered as a biological variable.	Tested between P41-47.	Less time in light compartment of light/dark box. Less OAT% for EPM.	Pups were exercised 30 min per day from P21-40. Improved TLC and OAT%.	Vathy et al. (1985)
Ahmadalipour et al. (2015)	E11-18 2x daily. First 3 injections 5 mg/kg, remaining injections 10 mg/kg. SubQ.	Cross-fostered so each mother raised half-saline and half morphine-exposed pups. Litters reduced to 10 maximum, with an equal sex balance. One saline-exposed and one morphine-exposed pup per sex per dam was selected for behavioral testing. Data collapsed across sexes due to high Pearson's correlation.	Tested between P51-57.	Smaller time in light compartment/entries into light compartment on L/D box. Lower OAT on EPM. Lower STL. Higher TDC. Lower BDNF levels.	Enrichment from P21-50. Improved OAT, STL, TDC, and BDNF.	Vathy et al. (1985)
Laborie et al., 2005	E11-18 2x daily 10 mg/kg. SubQ.	Litters reduced to 10 maximum. Only male rat pups tested.	Tested at 3 months age.	Decreased basal adrenal NE content. Lower basal adrenal PNMT, which did not respond to ether stress. Increased hippocampal 5HT/5H1AA after ether stress. Increased hypothalamic basal 5HT/5H1AA. Increased hypothalamic 5H1AA after stress.	Maternal adrenalectomy improves HPA axis function.	Vathy et al. (1985) and Lesage et al. (1998)
Lesage et al. (1998)	E11-18 2x daily 6 mg/ml (20 mg/kg/day). SubQ.	No differences seen between male and female pups; pups pooled. Used 2–4 pups from some of the mothers in each group for experiments.	Tested at P0.	Adrenal atrophy/hypoactivity. Reduced CRF in the hypothalamus.	Maternal adrenalectomy at E10 minimizes effects of maternal opiate exposure on the HPA axis.	N/A
Rimanóczy and Vathy, 1995	E11-18 2x daily. First 2 injections 5 mg/kg, remaining injections 10 mg/kg. SubQ.	Cross-fostered so each mother raised half saline and half morphine-exposed pups. Litters adjusted to 8–10 pups. One male and one female from each litter used. All females OVX.	OVX ∼ 7–10 days before sacrifice. Tested at P75-85.	Estradiol only affects hypothalamic Bmax of mu opioid receptors in morphine exposed OVX females.	N/A	Vathy and Katay (1992) (cites Vathy et al., 1985) and Vathy et al., 1994 (cites Vathy et al., 1983; Vathy et al., 1985; Vathy and Katay, 1992)
Rimanóczy et al., 2003	E11-18 2x daily. First 3 injections 5 mg/kg, remaining injections 10 mg/kg. SubQ.	Cross-fostered so each mother raised half- saline and half morphine-exposed pups. Litters reduced to 10 maximum, with an equal sex balance. One saline-exposed and one morphine exposed male pup per litter was selected for analysis.	Tested between P60-90.	Smaller stress-induced increased in ACTH for males.	N/A	Vathy et al. (1983) and Vathy et al. (1985)
Šlamberová et al., 2004	E11-18 2x daily. First 3 injections 5 mg/kg, remaining injections 10 mg/kg. SubQ.	Cross-fostered so each mother raised half- saline and half morphine-exposed pups. Litters reduced to 10 maximum. One saline-exposed and one morphine exposed female pup per litter was selected for analysis.	Tested between P60-90.	Smaller stress-induced increase in ACTH.	N/A	Vathy et al. (1985)
Šlamberová et al. (2002)	E11-18 2x daily. First 3 injections 5 mg/kg, remaining injections 10 mg/kg. SubQ.	Cross-fostered so each mother raised half- saline and half morphine-exposed pups. Litters reduced to 10 maximum, with an equal sex balance. One saline and one morphine-exposed male or female used from each litter.	OVX at P60. Tested between P70-90.	Males showed more struggling and less swimming on the forced swim, as well as an increased number of squares visited along walls after cold water stress. OVX females showed less grooming on the open field.	N/A	Vathy, 1995; Vathy et al. (1985)
Vathy et al., 2000	E11-18 2x daily. First 3 injections 5 mg/kg, remaining injections 10 mg/kg. SubQ.	Cross-fostered so each mother raised half saline and half morphine-exposed pups. Litters adjusted to 10 pups. Both males and females used. All females OVX.	OVX at P60. Tested at P65-75.	Increased TH-IR in male caudal PVN/LC. Decreased TH/IR in female LC. Estradiol does not affect LC TH-IR in morphine-exposed females.	N/A	Vathy and Katay (1992) (cites Vathy et al., 1985)