Intracerebroventricular Oxytocin Self-Administration in Female Rats

Abstract

Oxytocin (OT) is a neuromodulator that facilitates pair-bonding, maternal care and social approach. OT is considered to promote these social behaviours by enhancing the salience and reinforcing effects of relevant social stimuli. There is the additional possibility that OT per se may be rewarding. To test this, we investigated whether female rats would voluntarily self-administer OT. Female Long-Evans rats were ovariectomised and then received an oestrogen implant and an i.c.v. cannula. Rats were tested in an operant chamber with active and inactive levers. They were initially tested for 4 h/day on a fixed-ratio 5 schedule for self-administration of artificial cerebral spinal fluid (aCSF) for 5 days, followed by aCSF, or OT, at 1 or 10 ng/μl for another 5 days. Rats self-administering aCSF made 36.2 ± 6.2 active lever responses/4 h versus 14.9 ± 3.4 inactive responses. Responses for 1 ng/μl OT were similar. However, rats self-administering 10 ng/μl OT made significantly more active lever responses (67.8 ± 12.0 per 4 h), and received 121.4 ± 21.0 ng OT/4 h. To determine whether reduced anxiety contributes to the reinforcing effects of OT, rats received an infusion of aCSF or OT at 0.3 or 3.0 μg immediately before testing on the elevated plus maze. There was no effect of OT on anxiety as reflected by percentage time spent on the open arms, as well as no effect of OT on locomotion as measured either by the number of closed arm entries or the number of total arm entries. These results suggest that OT may be rewarding, and that this is not a result of the anxiolytic effects of OT.

Keywords: intracerebroventricular; operant behaviour; oxytocin; rats; reinforcement; self-administration.

Fig. 1

Operant responses/4h for icv infusion of OT in female rats. Responses at FR5 (mean±SEM) for active (closed bars) and inactive (open bars) levers averaged over 5 days. By RM-ANOVA, there was a significant effect of OT and a significant effect of lever on operant responses. Asterisk indicates significant increase in active lever responses for OT at 10 ng/ul vs vehicle (0 ng/ul OT).