Chronic moderate hyperglycemia does not alter sexual motivation in the female rat.

The relationship between diabetes mellitus type 2 (DM2) and sexual desire in women has not been systematically studied, therefore, animal models have been used for this purpose. When streptozotocin (STZ) is administered in the neonatal stage, the rat shows moderate chronic hyperglycemia and glucose intolerance in adulthood, resembling a DM2 model. These females show less alterations of sexual behavior (a slight decreased proceptivity and loss of paced mating) than their counterpart with severe hyperglycemia. However, the motivational components of copulation in female rats in this DM2 model have not been examined. The aim of this study was to evaluate female sexual motivation in a model of DM2 in three behavioral paradigms: the partner preference (PP), the sexual incentive motivation (SIM) and the odor preference test (OPT) tests. Neonatal females (3-4 days) were administered with streptozotocin (STZ, 70 mg/kg, intraperitoneally) or citrate buffer. At week 8, a glucose tolerance test was performed, females with blood glucose levels ≥ 250 mg/dl 60 min after a sucrose load (2 g/kg) were considered for the study. Behavioral tests were conducted at week 12, when the females were in natural proestrus. For PP we registered the time in each compartment and the sexual behavior, while in the SIM test, we calculated the time the females remained in each incentive zone. In these tests a castrated male and a sexually experienced male were used as stimuli. In OPT we evaluated the time the females spent sniffing the sawdust coming from cages housing these stimuli. In the PP and OPT hyperglycemic females behave similarly than controls, i.e., they retain a preference for sexually active males. In the SIM test there was a decrease in the time the hyperglycemic females remain in the vicinity of the sexually expert male. Data are discussed on the bases of the accessibility of the females to the stimuli.

Does Chronic Hyperglycemia Affect Female Rat Sexual Behavior? Differences in Paced and Non-Paced Mating.

INTRODUCTION: Diabetes mellitus has been associated with sexual dysfunction; however, in women this relationship is controversial. A study using a model of type 2 diabetes mellitus (DM2) failed to find a reduced receptivity in the non-paced mating (NPM), but the appetitive aspects of female sexual behavior have not been evaluated, for example, in the paced mating (PM) paradigm. AIM: To evaluate all components of female sexual behavior (in NPM and PM) in a model of DM2 using ovariectomized (OVX) (treated with steroids) or intact female rats (non-OVX) in natural proestrus. METHODS: Neonatal females (3-4 days) were administered streptozotocin (STZ, 70 mg/kg, intraperitoneally) or citrate buffer. At week 8, a glucose tolerance test was performed. At week 10, half of the females were OVX, and in the other half (non-OVX) the estrous cycle was monitored. At the twelfth week, the sexual behavior tests were conducted; OVX females were treated with estradiol benzoate (10 µg, -24 hours) and progesterone (3 mg, -4 hours), whereas the non-OVX were evaluated on vaginal proestrus. MAIN OUTCOME MEASURES: We registered in NPM and PM receptivity (lordosis quotient and intensity), as well as the number of proceptive and aggressive behaviors. Additionally, in PM we calculated the percentage of exits and the return latencies after receiving stimulation and the time the female remained in the male's compartment. RESULTS: The STZ-treated females presented glucose intolerance and were hyperglycemic. Neonatal STZ treatment provoked changes in the females' sexual behavior depending on the paradigm and the hormonal condition. In the NPM, STZ-OVX females had decreased lordosis quotient and intensity and increased aggression, whereas, in the STZ-non-OVX females, there was a decrease in proceptivity; such changes were not observed in PM. Regardless of whether the STZ-treated females were OVX, they failed to perform the pacing behavior. CLINICAL IMPLICATION: These data support the idea that chronic mild hyperglycemia, like that observed in DM2 (which represents 90% of the clinical cases), provokes marginal changes in most aspects of female sexual behavior. STRENGTHS & LIMITATIONS: The main strength of this work is the evaluation of consummatory and motivational aspects of female sexual behavior in a model of DM2. The main limitation is the duration of the experimental design that does not resemble the course of the disease in humans. No histologic or biochemical analyses were performed. CONCLUSION: These results suggest that chronic hyperglycemia produces decreases in sexual behavior. Hernández-Munive AK, Rebolledo-Solleiro D, Fernández-Guasti A. Does Chronic Hyperglycemia Affect Female Rat Sexual Behavior? Differences in Paced and Non-Paced Mating. J Sex Med 2019;16:1130-1142.

Reduced Lordosis and Enhanced Aggression in Paced and Non-Paced Mating in Diabetic Female Rats.

BACKGROUND: Clinical studies have shown altered sexual function in people with diabetes; basic science studies, using the streptozotocin (STZ)-induced animal model of type 1 diabetes mellitus (DM1), have consistently reported decreased sexual behavior in hyperglycemic female animals, but features of sexual motivation and aggressive behavior have not been explored in these animals. AIM: To study several parameters that denote sexual motivation in STZ-treated female rats and to compare behavioral features of sexual behavior and aggression in non-paced mating (NPM) and paced mating (PM) conditions. METHODS: DM1 was induced by injecting STZ (diluted in citrate buffer) at a dose of 50 mg/kg intraperitoneally over 2 consecutive days into ovariectomized Wistar rats. 10 days later, female rats were treated with estradiol benzoate (10 µg, -24 hours) and progesterone (3 mg, -4 hours); their sexual behavior (including lordosis quotient, lordosis intensity, and proceptivity) and aggression were evaluated under NPM and PM conditions. Body weight, blood glucose levels, and spontaneous ambulatory activity also were measured. A group of STZ-treated animals was administered a long-acting insulin analogue (glargine) every 12 hours for 8 days, and their sexual and aggressive behaviors were evaluated in NPM. OUTCOMES: We quantified body weight, blood glucose level, spontaneous ambulatory activity, and sexual and aggressive behaviors in NPM and PM; the time the female rats spent interacting with the male rat or in the male rat's chamber also was registered in PM. RESULTS: Compared with controls, STZ-treated ovariectomized rats lost body weight, had increased blood glucose levels, and had unchanged spontaneous ambulatory activity. In the PM and NPM conditions, animals showed decreased lordosis quotient and lordosis intensity, increased aggression, and unaltered proceptivity, although in NPM the effects of STZ treatment on aggression were more drastic and were completely prevented by insulin. In PM no differences were found between diabetic and control female rats in the time interacting with the male rat or in the male rat's chamber. CLINICAL TRANSLATION: These findings support the observation of increased prevalence of sexual dysfunctions and aggression in the clinical setting of DM1. STRENGTHS AND LIMITATIONS: The main strength of this study is that it analyzed sexual behavior under PM and NPM conditions and aggression in STZ-treated female rats. Its main limitations are that the model of DM1 represents only 10% of the affected population and that no specific treatment is proposed for the sexual dysfunctions. CONCLUSION: These results suggest that STZ-treated rats have decreased sexual receptivity in NPM and PM, accompanied by increased aggressiveness in NPM. Hernández-Munive AK, Rebolledo-Solleiro D, Ventura-Aquino E, Fernández-Guasti A. Reduced Lordosis and Enhanced Aggression in Paced and Non-Paced Mating in Diabetic Female Rats. J Sex Med 2018;15:124-135.