Effects of the Estrous Cycle on Ultrasonic Vocalization in Response to Amphetamine

Human and animal research suggests the existence of sex differences in drugs of abuse where females are more susceptible to drug addiction; however, the risk factors and vulnerability to drug abuse in female subjects have not been explicitly investigated party because of the fluctuating levels of gonadal hormones in females. Ironically, one of the gonadal hormones, estrogen, may play a significant role in heightened vulnerability to drug abuse in females. Some studies examine this possibility with ovariectomized females given estradiol in replacement of estrogen. However, the removal ovaries may induce unnatural responses to drugs of abuse in female subjects. Therefore, this study utilizes female rats with intact ovaries to study the effects of endogenous estrogen levels in their initial response to amphetamine. When stimulated by drugs of abuse, rats emit 50-kilohertz (kHz) range frequency-modulated ultrasonic vocalizations (USVs) to expressively indicate their euphoric state. The USVs will serve as a proxy measure to determine subjects’ initial response to amphetamine in each of the phase of the estrous cycle. Each phase of the estrous cycle is marked by unique vaginal epithelial cells and levels of estrogen where the proestrus and estrus phases exhibit the peak levels of estrogen as compared to the diestrus and metestrus phases. Therefore, the USV calls are expected to be the highest in rats who are in proestrus and estrus phases of the estrous cycle upon initial amphetamine injection. The results indicate that amphetamine induces heighted number of USV calls compared to saline and that the proestrus and estrus phases of naturally cycling female rats only marginally affect the USV calls in initial response to amphetamine. Even though the data suggest a potential role of the estrous cycle on the expression of euphoric 50-kHz USV calls upon initial injection of amphetamine, more studies are needed to confirm this finding.