Table 1.
Effects of OT on opioid‐induced, addiction‐related, behaviours
| Addictive substance | Administration paradigm | Animal model | Oxytocin administration paradigm | Effect of oxytocin | Reference |
|---|---|---|---|---|---|
| Morphine | Morphine tolerance: 37.5 mg morphine.HCl pellet, s.c. 48 h−1 | Male CFLP mice (25 ± 5 g) housed in groups | OT: 50 μg and 100 μg per animal, s.c. (2 h prior to morphine pellet implantation) | ↓development of tolerance | (Kovacs et al., 1985c) |
| Morphine tolerance: 30 mg·kg−1 morphine.HCl, s.c. and 5 h later 5 mg·kg−1 morphine.HCl, s.c. | Male albino inbred mice (25 ± 5 g) housed in groups | OT: 1 μg i.c.v. or intra‐CPu (1 h prior the tolerance‐inducing dose of morphine) | ↔ development of tolerance | (Sarnyai et al., 1988) | |
| Morphine tolerance: 30 mg·kg−1 morphine.HCl, s.c. and 5 h later 5 mg·kg−1 morphine.HCl, s.c. | Male albino inbred mice (25 ± 5 g) housed in groups | OT: 1 μg microinjection into: posterior olfactory nucleus, Central nucleus of the amygdala, ventral hipoccampus (1 h prior the tolerance‐inducing dose of morphine) | ↓ development of tolerance | (Sarnyai et al., 1988) | |
| Morphine tolerance: 60 mg·kg−1 morphine.HCl, s.c. and 5 h later 1 mg·kg−1 morphine.HCl, s.c. | Male CFLP mice (25 ± 5 g) housed in groups | OT: 2 μg·kg−1, s.c. (1 h prior the tolerance‐inducing dose of morphine) | ↓ development of tolerance | (Kovacs et al., 1987b) | |
| Morphine tolerance: 100 mg·kg−1 morphine.HCl, s.c. and 5 h later 1 mg·kg−1 morphine. HCl, s.c. | Male CFLP mice (25 ± 5 g) in groups | OT: 2 μg ·kg−1, s.c. (1 h prior the tolerance‐inducing dose of morphine) | ↓ development of tolerance | (Kovacs et al., 1987b) | |
| Morphine tolerance: 37.5 mg morphine.HCl pellet, s.c. 48 h−1 then, morphine.HCl (5 mg·kg−1, s.c.) | Male CFLP mice, housed in groups | OT: 50 μg, s.c. (24 h prior to pellet implantation) | ↓ development of tolerance | (Kovacs et al., 1984) | |
| Morphine tolerance: 37.5 mg per morphine.HCl pellet, s.c. 48 h−1 then, morphine.HCl (5 mg·kg−1, s.c.) | Male CFLP mice, housed in groups | OT: 5 ng or 0.5 μg·in 1 μL, i.c.v. (24 h prior to pellet implantation) | ↓ development of tolerance | (Kovacs et al., 1984) | |
| Morphine tolerance: 37.5 mg morphine.HCl pellet, s.c. 48 h−1 then, morphine.HCl (5 mg·kg−1, s.c.) | Male CFLP mice, housed in groups | OT: 0.5 ng in 1 μL into the dorsal Hip or the Acb (24 h prior to pellet implantation) | ↓ development of tolerance | (Kovacs et al., 1984) | |
| Morphine tolerance: 37.5 mg morphine.HCl pellet, s.c. 48 h−1 then, morphine.HCl (5 mg·kg−1, s.c.) | Male CFLP mice, housed in groups | OT: 0.5 ng in·1 μL, into the CPu, VTA or external cortical surface (24 h prior to pellet implantation) | ↔ development of tolerance | (Kovacs et al., 1984) | |
| Morphine‐induced conditioned‐place preference: Acquisition: 3 conditioning days (morphine. HCl, 5 mg·kg−1·day−1, s.c.) | Male Wistar rats (250–300 g), housed in groups | OT: 0.2 μg, i.c.v., 5 min prior to each conditioning session (both prior to morphine and prior to saline injections) | ↔ acquisition of morphine CPP | (Moaddab et al., 2015) | |
| Morphine‐induced conditioned‐place preference: Expression: 3 conditioning days (morphine. HCl, 5 mg·kg−1·day−1, s.c.) | Male Wistar rats (250–300 g), housed in groups | OT: 0.2 μg, i.c.v., 5 min prior to the post‐conditioning session | ↑ expression of morphine CPP | (Moaddab et al., 2015) | |
| Physical signs following precipitated withdrawal: Day 1: 2 x 20 mg·kg−1, i.p. Days 2–4: 2 x 40 mg·kg−1 i.p. (morning and afternoon injections) Naloxone: 4 mg·kg−1, i.p. (1 h after the morning morphine injection daily) | Female Wistar rats (130–150 g) housed individually | OT: 1.0 μg per animal, s.c. (1 h prior to each morphine injection daily) | ↑ physical dependence (decreased body weight) | (van Ree and de Wied, 1976) | |
| Naloxone‐precipitated withdrawal: 37.5 mg morphine.HCl pellet, s.c. 74 h−1 Naloxone (74 h after pellet implantation): 1 mg·kg−1, i.p. | Male CFLP mice, housed in groups | OT: 50 μg, s.c., (24 h prior to pellet implantation) | ↑ latency of naloxone‐precipitated withdrawal | (Kovacs et al., 1984) | |
| Naloxone‐precipitated withdrawal: 37.5 mg morphine.HCl pellet, s.c. 74 h−1 Naloxone (74 h after pellet implantation): 1 mg·kg−1, i.p. | Male CFLP mice, housed in groups | OT: 5 ng or 0.5 μg·in 1 μL, i.c.v. (24 h prior to pellet implantation) | ↑ latency of naloxone‐precipitated withdrawal | (Kovacs et al., 1984) | |
| Naloxone‐precipitated withdrawal: 37.5 mg morphine.HCl pellet, s.c. 74 h−1 Naloxone (74 h after pellet implantation): 1 mg·kg−1, i.p. | Male CFLP mice, housed in groups | OT: 0.5 ng in·1 μL into the dorsal Hip or the mesolimbic Acb (24 h prior to pellet implantation) | ↑ latency of naloxone‐precipitated withdrawal | (Kovacs et al., 1984) | |
| Naloxone‐precipitated withdrawal: 37.5 mg morphine.HCl pellet, s.c. 74 h−1 Naloxone (74 h after pellet implantation): 1 mg·kg−1, i.p. | Male CFLP mice, housed in groups | OT: 0.5 ng·in 1 μL into the CPu, VTA or external cortical surface (24 h prior to pellet implantation) | ↔ latency of naloxone‐precipitated withdrawal | (Kovacs et al., 1984) | |
| Naloxone‐precipitated withdrawal: 37.5 mg morphine.HCl pellet, s.c. 72 h−1 Naloxone (72 h after pellet implantation): 1 mg·kg−1, i.p. | Male CFLP mice (25 ± 5 g) housed in groups | OT: 50 μg and 100 μg per animal, s.c. (2 h prior to morphine pellet implantation) | ↓ withdrawal symptoms | (Kovacs et al., 1985c) | |
| 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 | Carbetocin: 6.4 mg·kg−1, i.p. (15 min prior to FST, EPM 5 min−1 prior to 3‐CB test/ | ↓ withdrawal‐induced depressive‐, anxiety‐like behaviours, sociability deficits | (Zanos et al., 2014a) | |
| Stress‐induced reinstatement morphine CPP: 10 mg·kg−1, s.c., for 4 conditioning days (morphine sulphate in the afternoon) Stress: forced‐swim stress (6‐min total) | Male C57BL/6 J mice (20–25 g), housed individually | Carbetocin: 6.4 mg·kg−1, i.p. (5 min prior to swim stressor for reinstatement) | ↓ stress‐induced reinstatement of morphine conditioned place preference | (Zanos et al., 2014a) | |
| Priming‐induced reinstatement of morphine CPP: 10 mg·kg−1, s.c., for 4 conditioning days (morphine sulphate in the afternoon) Priming: 2 mg·kg−1, i.p. (morphine sulphate) | Male C57BL/6 J mice (20–25 g), housed individually | Carbetocin: 6.4 mg·kg−1, i.p. (5 min prior to morphine priming injection) | ↓ morphine‐primed induced reinstatement of morphine conditioned place preference | (Georgiou et al., 2015b) | |
| Heroin | Self‐administration: 5 days of fixed ratio schedule of reinformcement: 0.25 mL of heroin solution (0.125 mg·mL−1 per infusion), i.v.; experimenter delivered two initial heroin injections by pressing the lever | Male Wistar rats (200–230 g) housed individually | OT: 1.0 μg per animal, s.c. (1 h prior to experimentation daily) | ↑ self‐administration (slightly) | (Van Ree and De Wied, 1977) |
| Self administration: 0.05 mg·kg−1·s−1.c., 2 × daily·4 days−1 +0.4 mg·kg−1, s.c., 2 × daily·3 days−1 Followed by 7 days of progressive ratio schedule of reinforcement: 0.25 mL of heroin solution (0.125 mg·mL−1 per infusion), i.v. | Male Wistar rats (200–220 g) housed individually | OT: 1.0 μg per animal, s.c. (1 h prior to self‐administration session on the day 7) | ↓ self‐administration | (Kovacs and Van Ree, 1985) | |
| Development of heroin tolerance (escalating‐dose): 2 x daily i.p. injections (100, 200, 400, 800, 800, 800 μg·kg−1) Self‐administration: On day 7 of heroin injections, rats were placed in self‐administration chambers; fixed‐ratio reinforcement: 50 μL of heroin solution (0.4 g·L−1) – flow rate 5 μL s; schedule terminated upon stable level of responding for 3 consecutive days (usually 7–8 days) | Male Sprague–Dawley rats (250 ± 30 g) housed individually | OT: intra‐accumbal or injections directly into the ventral Hip; 2 ng; treatment block of saline/OT/saline/OT 1.0 μg per animal, s.c. (1 h prior to self‐administration session daily) | ↓ self‐administration | (Ibragimov et al., 1987) |
A detailed summary of the effects of OT or OT‐based drugs administration on the behavioural effects of opioids in rodents. ↑ increase; ↓ decrease; ↔ no effect. Acb, nucleus accumbens; CPu, caudate‐putamen; Hip, hippocampus; VTA, ventral tegmental area.