Table I.

Summary of the effects of oxytocin on opiate-induced behaviors

Behavior	Effect	OT dose (per animal or / kg)	Route	Interval OT→Opiate (minutes)	Opiate dose	Species	OT repeate d	OT ICV* *	OTA reverses effect	Site of action	Reference
MORPHINE
Acute tolerance to analgesia	↓	0.0005, 0.005*, 0.05*, 5*,50* μg	sc	60	100 mg/kg	mice	No	Yes	Yes	ns	(58, 59)
Chronic tolerance to analgesia	↓	0.5,5.0,50*, 100*μg	sc	120	pellet 37.5 mg sc	mice	No	Yes	ns	HC, NAc	(59, 60)
Withdrawal (naloxone)	delay	0.5,5.0,50*, 100*μg	sc	120	pellet 37.5 mg sc	mice	No	Yes	ns	HC, NAc	(59, 60)
Anxiety, Depression post withdrawal	↓	Carbetocin 6.4mg/kg	ip	Post 7d withdrawal	20mg/kg→100mg/kg/ day x 7 d	mice	No	ns	ns	ns	(37)
Social behaviors post withdrawal	↑
Conditioned Place Preference(CPP):
Acquisition	↔	0.2μg or OTA alone	icv	5	5mg/kg sc	rats	Dailyx 3d	ns	ns	ns	(65)
Expression	↑	0.2μg	icv	n/a	5mg/kg sc		No	ns	No	NAc shell	(65)
Reinstatement by stress	↓	Carbetocin 6.4mg/kg	ip	n/a	n/a	mice	n/a	ns	ns	ns	(37)
HEROIN
Tolerance to analgesia:
Single dose	↓	2–200μg/kg day1 or 4	sc	60	800μg/kg	mice	No	ns	ns	ns	(62)
Repeated doses	↓	2–200μg/kg		60	800μg/kg		Dailyx 4d		ns	ns	(62)
Self-administration:
Heroin naïve	↔	0.5μg	sc	60	0.02mg/ infusion	rats	Dailyx 8d	ns	ns	ns	(63)
Heroin tolerant
Acquisition	↓	0.5*μg	sc	60	0.02mg/ infusion	rats	Dailyx 8d	ns	ns	ns	(63)
Maintenance	↓	0.05, 0.5*, 5.0* ug	iv	60	0.02mg/ infusion	rats	No	ns	ns	NAc; HC***	(63, 104)

↓= Decreased; ↑= Increased; ↔= no effect; *= dose producing significant effect; OT=oxytocin; OTA=OT receptor antagonist; sc=subcutaneous; ip=intraperitoneal; icv= Intracerebroventricular; iv=intravenous; HC=hippocampus; NAc=Nucleus Accumbens; n/a=not applicable

Carbetocin: OT analogue; d: day; ** results reproduced with icv OT administration; *** Duration of effect=24h; ns: not studied