Abstract

Oxytocin has a modulatory role in natural and drug reward processes. While the role of oxytocin in pair bonding and reproduction has been extensively studied, sex differences in conditioned and unconditioned behavioral responses to oxytocin treatment have not been fully characterized. Here, we determined whether male and female rats would show similar dose response curves in response to acute oxytocin on measures of locomotor activity, sucrose seeking, and sucrose intake. Male and freely cycling female rats received vehicle or oxytocin (0.1, 0.3, 1, 3mg/kg, IP) injections before behavioral tests designed to assess general motor activity, as well as sucrose self-administration and seeking. Lower doses of oxytocin decreased motor activity in a novel environment in females relative to males. Likewise, lower doses of oxytocin in females decreased responding for sucrose during maintenance of sucrose self-administration and reinstatement to sucrose-conditioned cues. However, sucrose seeking in response to a sucrose prime was only decreased by the highest oxytocin dose in both sexes. In general, oxytocin had similar effects in both sexes. However, females were more sensitive to lower doses of oxytocin than males. These findings are consistent with the notion that oxytocin regulates many of the same behaviors in males and females, but that the effects are typically more profound in females. Therapeutic use of oxytocin should include sex as a factor in determining dose regimens.

Highlights

  • Oxytocin is a classical and well-characterized neuroendocrine hormone that is a potent modulator of a variety of brain functions, including emotions, social interactions, and sexual behavior [1]

  • There was a sex × oxytocin dose interaction [F(4,81)=2.64, p

  • We have established sex differences in the dose response of oxytocin on locomotor activation, lever responding for sucrose, and sucrose seeking

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Summary

Introduction

Oxytocin is a classical and well-characterized neuroendocrine hormone that is a potent modulator of a variety of brain functions, including emotions, social interactions, and sexual behavior [1]. Oxytocin is primarily synthesized in magnocellular neurons of the supraoptic and paraventricular nuclei of the hypothalamus and is secreted by axon terminals in the posterior pituitary into systemic blood circulation [3]. Oxytocin is produced in parvocellular and magnocellular neurons in the paraventricular nucleus that project to various brain regions and release oxytocin [4]. Acting oxytocin has a number of behavioral and physiological effects, including suppression of food intake [5]. Peripheral injection of oxytocin in rats inhibits sucrose intake, whereas oxytocin receptor antagonists increase consumption [6, 7]

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