Evaluation of The Research Methods on Different Specimen and Sex Dissimilarities in Clinical Tests

Extensive research on addiction has given rise to several models and theories. While there is still a lot to be learned about addiction we know that factors like the environment, gender, and genetics play in a role in how an addiction develops. Cocaine addiction studies commonly use rats in order to predict human addiction issues. Studies focusing on cocaine have revealed many of the reasons behind how and why cocaine is addictive and have given us insight into the genetic and psychological factors that contribute to cocaine use.

“The Development of a Preference for Cocaine over Food Identifies Individual Rats with Addiction-Like Behaviors” was conducted under the rationale that cocaine dependence is characterized by compulsive drug use that replaces one’s recreational, occupational and social parts of life. This study hypothesized that rats preference for cocaine over food rewards could predict how vulnerable each rat was to addiction. This study used self-administration that was allowed on a fixed-ratio schedule with cocaine-only, pellet-only and choice sessions. Motivation for each reward was given early and late during self-administration using a progressive-ratio schedule. The reinstatement of cocaine- and pellet-seeking was examined following exposure to the given cues. The findings from this study showed that cocaine-preferring rats increased their drug intake at the expense of pellets, and displayed increased motivation for cocaine. Also, females showed an increased likelihood for developing cocaine preferences. This study confirms that the choice self-administration paradigm is a valid model of addiction. The sex-specific vulnerability factors were differentiated from the rat’s generalized sex differences in behavior, which suggests that the neurobiology of addiction could be different between genders. The cocaine-preferring rats displayed changes in behavior that mimicked many of the symptoms that are used in the diagnosis of addiction in humans, including an increased frequency of drug taking and decreasing participation in previously enjoyed activities. This experiment was one of the first to show that that preferences for cocaine over food rewards can represent an “addicted” phenotype. However other studies have shown that high doses of cocaine are not preferred over food when longer intervals are used (Kerstetter et al., 2012).

The rationale behind the study “Gender differences in clinical outcomes for cocaine dependence: Randomized clinical trials of behavioral therapy and disulfiram” is that despite a large amount of research having been conducted on gender differences in addiction, there are few published reports that compare treatment outcomes for women versus men based on treatments evaluated in randomized clinical trials. The study used a large sample that incorporated data from five randomized clinical trials of treatment for cocaine dependence. This sample was evaluated for gender differences in the clinical outcomes. A secondary analysis compared gender differences in outcome by medication condition (disulfiram vs. no medication) and across multiple behavioral treatment settings. The results showed that when compared with men, women had poorer treatment outcomes on multiple measures of cocaine use during treatment and at post-treatment follow-up. The study states that these gender differences are primarily due to disulfiram being less effective in women compared with men. There was no evidence of gender differences in outcome as a function of the behavioral therapies evaluated. These results suggest that women and men may benefit from the same behavioral treatments for addiction. However, some addiction pharmacotherapies, like disulfiram, may lead to poorer outcomes among women relative to men. This creates a need for careful assessment of pharmacological treatments in both sexes prior to widespread clinical implementation.

Using rats serves as a good model for research as they share a lot of the structure and connectivity that exists in human brains. However there is a lot of variability in rats when it comes to personality and genetic risk factors. Rats cannot communicate with researchers about how they feel, so determining when a rat is addicted to a substance can be more complicated. Rats have no driving force, like people may, to cut down or control their substance use when exposed to drugs. The similarities between rats and humans can be seen in the two studies above. The first study used rats as a subject and came to the conclusion that the neurobiology of addiction could be different between genders. This idea agrees with the second studies finding that some pharmacotherapies, like disulfiram, may lead to poorer outcomes among women than men. However, when using behavioral therapies there are very little gender differences. Other randomized control studies have shown that modafinil (Dackis et al., 2012) and naltrexone plus CBT/medication management (Pettinati et al., 2008) result in improved cocaine outcomes in men relative to a placebo, but women have a tendency towards worse outcomes on medication relative to a placebo. When looking at the findings of these studies, it raises the issue that there may be large differences in how men and women respond to pharmacotherapies, and possibly other types of therapy. More research needs to be done in order to see if the female preference for cocaine over food rewards is also due to the “addicted” phenotype that was seen in rats.

When viewing the results of both of these studies together it’s apparent that the treatment needs of women may be different from those of men. Women do have a lower rate of substance use and dependence than men (SAMHSA, 2004) and only account for approximately 32% those in substance use treatments (Brady and Ashley, 2005). This difference could lead to well-controlled trials, which include both genders, to be more representative of men's treatment response. When overgeneralizing the results from studies of one gender there is the risk of suboptimal treatment efficacy for the insufficiently studied gender (Nieuwenhoven and Klinge, 2010). There is a need to research and consider the gender-sensitive effects of established treatments. While behavioral treatments appear to be successful for men and women, pharmacological treatments tend to be less effective for treating cocaine dependence in women. Research should more consistently incorporate gender difference analyses. Ongoing research is needed to look into the mechanisms of actions for behavioral and pharmacological therapies, since recent studies have suggested gender differences in the mechanisms that contribute to the development and maintenance of cocaine use.