Table 2.
Effects of opioids on the oxytocinergic system
| Treatment | Addiction phase | Administration paradigm | Animal model | Effect on oxytocin | Reference |
|---|---|---|---|---|---|
| Morphine | Acute | 4 μg, i.v. | Lactating Wistar rats | ↓ hypothalamic OT release | (Clarke et al., 1979) |
| 10 mg·kg−1, s.c. | Swiss Webster mice between the 11th and 22nd day of lactation | ↓ OT release during suckling | (Haldar and Sawyer et al. 1978) | ||
| 5 mg·kg−1, s.c. | Male CFLP mice (25 ± 5 g) housed in groups | ↑ OT immunoreactivity in Hip, Amy and basal forebrain | (Kovacs et al. 1987a) | ||
| 5 mg·kg−1, i.v. | Virgin Sprague–Dawley female rats (~270 g) |
↓ spontaneous activity of SON OT neurons ↓ plasma OT levels |
(Pumford et al., 1991) | ||
| 0.1–1.5 μg·μL−1, i.c.v. | Virgin Sprague–Dawley female rats (~300 g) | ↓ spontaneous activity of SON OT neurons | (Pumford et al., 1991) | ||
| Chronic | Morphine pellet (37.5 mg morphine.HCl), s.c. | Male CFLP mice (25 ± 5 g), housed in groups | ↔ OT immunoreactivity in Amy and basal forebrain | (Kovacs et al. 1987a) | |
| Osmotic mini‐pump (75 mg), s.c., 1 on day 0, 2 on day 2 and 3 on day 4. On day 8 morphine.HCl (30 mg·kg−1.i.p.) | Male Sprague–Dawley rats (230–270 g) housed in groups |
↓ OT immunoreactivity in the Hip, SON, ME and ARC ↓ OT peptide levels in SON and ME ↔ OT peptide levels in PVN |
(Laorden et al., 1997; Laorden et al., 1998) | ||
| Osmotic mini‐pump, s.c., 10 μg·h−1·40 h−1 then 20 μg h−1·40 h−1 and then 50 μg h−1·40 h−1 | Lactating, primiparous Sprague–Dawley female rats (2–4 days post‐partum) | ↔ plasma OT levels | (Bicknell et al., 1988) | ||
| Osmotic mini‐pump, s.c., 10 μg h−1·40 h−1 then 20 μg h−1·40 h−1 and then 50 μg h−1·40 h−1 | Virgin Sprague–Dawley female rats (~270 g) | ↔ firing rate of active non‐phasic OT neurons | (Pumford et al., 1991) | ||
| 20–100 mg·kg−1·day−1, for 7 days, i.p. morphine sulphate | Male C57BL/6 J mice (20–25 g), housed individually |
↑ OT receptor levels in the olfactory nuclei, PirCx and Amy ↓ hypothalamic OT levels |
(Zanos et al., 2014a) | ||
| Naloxone ‐Precipitated withdrawal |
Morphine: osmotic mini‐pump, s.c., 10 μg h−1·40 h−1 then 20 μg h−1·40 h−1 and then 50 μg h−1·40 h−1
Naloxone (day 5; following morphine administration): 5 mg·kg−1, i.v. |
Lactating, primiparous Sprague–Dawley female rats |
↑ plasma OT levels; ↑ firing rate of OT neurons (SON) |
(Bicknell et al., 1988) | |
|
Morphine sulphate (20–40 mg·kg−1) x 5 days, i.c.v (1 μL·h−1) Naloxone (day 5; after i.c.v. morphine): 5 mg·kg−1, i.v. |
Virgin Sprague–Dawley female rats (243–287 g) housed individually |
↑ plasma OT levels; ↑ OT levels in CSF |
(Coombes et al., 1991) | ||
|
Osmotic mini‐pump (75 mg), s.c., 1 on day 0, 2 on day 2, 3 on day 4. Naloxone.HCl 1 mg·kg−1, s.c. (on day 7) |
Male Sprague–Dawley rats (200–210 g) housed in groups | ↑ OT mRNA levels in the ME and PVN | (Laorden et al., 1998) | ||
|
Morphine: osmotic mini‐pump, s.c., 10 μg h−1·40 h−1, then 20 μg h−1·40 h−1, then 50 μg h−1·40 h−1
Naloxone (day 5; after last morphine infusion): 5 mg·kg−1, i.v. |
Virgin Sprague–Dawley female rats (~250 g) housed individually |
↑ plasma OT levels ↑ OT peptide levels in the mediolateral septum ↔ OT levels in the dorsal Hip ↔ OT levels in the nucleus of tractus solitarius |
(Russell et al., 1992) | ||
|
Morphine: osmotic mini‐pump, s.c., 10 μg h−1·40 h−1, then 20 μg h−1·40 h−1, then 50 μg h−1·40 h−1
Naloxone (day 5 after last morphine infusion): 5 mg·kg−1, i.v. |
Virgin Sprague–Dawley female rats housed individually | ↑ OT SON neuron post‐spike excitability in morphine‐dependent rats and to a lesser extend in morphine‐naïve rats | (Brown et al., 2005) | ||
| Spontaneous withdrawal |
20–100 mg·kg−1·day−1, for 7 days, i.p. morphine sulphate Withdrawal: 7 days in home cage without injections |
Male C57BL/6 J mice (20–25 g), housed individually | ↑ OT receptor levels in the olfactory nuclei, MS, VDB, LS, PirCx and Amy | (Zanos et al., 2014a) |
A detailed summary of the effects of opioid drugs on the oxytocinergic system. ↑ increase; ↓ decrease; ↔ no effect.
Abbreviations: Amy, amygdala; ARC, arcuate nucleus; Hip, hippocampus; LS, lateral septum; ME, median eminence; MS, medial septum; SON; supraoptic nucleus of the hypothalamus; PirCx, piriform cortex; PVN, paraventricular nucleus of the hypothalamus; VDB, ventral limb of the diagonal band of Broca.