Estrous Cycle Study Regarding Alcohol Use Disorder Through Endostatin Treatment

Abstract

Alcohol Use disorder has been defined as the chronic relapsing brain with an inability to stop or control alcohol use despite adverse social, occupational, or health consequences. 17 million Americans have met the criteria to be diagnosed as having moderate to severe alcohol use disorder in the past decade. Relapse to alcohol seeking has become a public health concern.An increased amount of PECAM‐1 in the medial Prefrontal Cortex has been shown to be linked to enhanced reinstatement of alcohol seeking. It was hypothesized that endostatin would decrease PECAM‐1 in the mPFC. It was also hypothesized that changes in the behaviour of female rodents with ethanol dependence who were treated using endostatin would be linked to their estrous cycles. Saline was used as the control vehicle in this experiment and endostatin as the variable. The rodents were divided into a control group with no alcohol dependence, a group with no alcohol dependence who were administered endostatin, and a group which was alcohol dependant who were also administered endostatin. Alcohol dependence was established by exposing the rats to ethanol vapor.The results found that in rodents with alcohol dependence, endostatin reduced relapse to drinking in female rats. The estrous cycle in female rats is comparable to menstruation in female humans. However, in rats, there are four phases: proestrus, estrous, metestrous, and diestrus. Estrous phase sample stains showed that Endostatin was not responsible for the changes in estrous phases. There was however, a significant change in estrous phases of rats with any form of alcohol consumption. Future research on this project will determine the underlying mechanisms of how exactly alcohol is able to alter the estrous cycles of rats. It will also determine the role of estrous phases in alcohol dependence. Additionally, endostatin can be research as a viable treatment for alcohol use disorder.Support or Funding InformationUCSD STARS Program ]MARC U STAR CSUB NIHFigure 3. (left panel); Drinking behavior in CIE female and male rats during baseline, CIE and relapse to drinking sessions. Female rats have higher ethanol intake during baseline sessions and this difference did not persist during CIE. There was a trend towards higher response during relapse session in females (right panel); Drinking behavior in CIE female and male rats during relapse session with or without endostatin treatment. There was a significant sex × endostatin interaction F (3, 93) = 2.751, p=0.04 and main effect of endostatin treatment F (3, 93) = 4.05, p<0.05 with females showing reduced drinking during relapse sessions after endostatin treatment. N=6 to 13 rats in each group. Data is expressed as mean +/− SEM.Figure 1Figure 2. (left panel); Drinking behavior in ED female and male rats during baseline, maintenance and relapse to drinking sessions. Female rats have higher ethanol intake during baseline sessions and this difference did not persist during maintenance. There were no differences during relapse session between males and females. (right panel); Drinking behavior in ED female and male rats during relapse session with or without endostatin treatment. There was no significant effect of endostatin in either sexes tested. N=6 to 13 rats in each group. Data is expressed as mean +/− SEM.Figure 2