Copulation-induced antinociception in female rats is blocked by atosiban, an oxytocin receptor antagonist

We hypothesized that copulation-induced temporary anti-nociception in female rats is mediated by the activation of central and/or peripheral oxytocin receptors. To test this hypothesis, we assessed the effects of intraperitoneal (ip), intrathecal (it), and intra-cerebroventricular (icv) administration of an oxytocin receptor antagonist (atosiban), on copulation-induced temporary anti-nociception in estrous rats. The treatment groups were ovariectomized rats pre-treated subcutaneously (sc) with 10 μg of estradiol benzoate (EB) followed 24 h later by an sc injection of 5 μg EB, and 4 h later, by an sc injection of 2 mg progesterone (P4). Rats were then administered saline vehicle (ip, it, or icv: control groups) or atosiban (500 μg/kg ip; 500 ng it; or 500 ng icv: experimental groups). Thirty minutes after drug or saline administration, their sexual behavior was tested by pairing with a sexually-experienced male rat. Brief pulse trains of 50 Hz, 300 ms duration, supra-threshold tail electrical shocks (STS) were delivered before and during copulatory activity i.e., while the female was receiving mounts, intromissions, or ejaculations, and we recorded whether vocalization occurred in response to each STS. Replicating our previous findings, the vocalization response to STS in control rats was significantly attenuated during intromissions and ejaculations, compared to their baseline (pre-mating) response, indicative of anti-nociception. By contrast, rats pre-treated with atosiban (each route of administration) failed to show an attenuation of the vocalization response to shock. These findings provide evidence that the temporary anti-nociceptive effect of copulation in female rats is mediated by copulation-induced release of endogenous oxytocin in brain, spinal cord and periphery. •Copulation induces antinociception in female rats.•Copulation-induced antinociception is reduced by atosiban administration.•Hence, oxytocin plays a significant role in mediating copulation-induced antinociception.