During my year as a research specialist under Dr. Wendy Lynch (2013), I ran a multi-experiment project investigating the effects of various pharmacological treatments on the reinforcing effects of alcohol. Specifically, I measured effects of combination of medications that modulate GABA, glutamate, opioid, and/or serotonin receptors on motivation and maintenance of ethanol self-administration.

While most currently available treatments for alcohol use disorders are single-pathway targeted pharmacotherapies, these have only shown modest therapeutic value. Combination medications are likely to have enhanced efficacy over the traditional single-medication approach by targeting multiple neurotransmitter pathways implicated in different components of this disorder.

I found that a low dose combination of naltrexone (a μopioid antagonist) and topiramate (a gamma-amino-butyric acid (GABA)/glutamate modulator) reduced ethanol intake and motivation with greater efficacy and fewer side effects than either alone. In another study investigating acute and chronic administration of topiramate and ondansetron (a serotonin-3 agonist), I found that chronic administration of the combination of these medications produced a persistent reduction in ethanol responding, an effect that outlasted topiramate alone. These studies support combination medications for the treatment of alcohol use disorders for both increased efficacy and the additional benefit of the ability to use low doses, which may be suboptimal on their own, but are effective when combined.

Additionally, we were the first to investigate sex differences in the efficacy of treatment with topiramate and naltrexone: pharmacological treatments that are either used or being investigated for use in humans. Specifically, we tested the effects of topiramate and naltrexone, alone or in combination, on the reinforcing properties of ethanol in male and female rats. In response to pharmacological treatment, we observed some sex differences and similarities, most notably, a more robust effect of the combination of naltrexone and topiramate in males as compared to females. This study also established this model of alcohol preferring-P rats as an effective and reliable preclinical model, a timely imperative for addiction research as clear gender differences exist in the use of alcohol and prevalence and severity of alcohol use disorders.

1. Moore CF, Lynch J. (2015), Alcohol Preferring (P) Rats as a model for examining sex differences in Alcohol Use Disorders and its treatment. Pharmacology, Biochemistry, and Behavior, 132, 1-9. PMCID: PMC4545742.

2. Moore CF, Lycas MD, Bond CA, Johnson BA, Lynch WJ. (2014), Acute and chronic administration of a low-dose combination of topiramate and ondansetron reduces ethanol’s reinforcing effects in male Alcohol Preferring (P) rats. Experimental and Clinical Psychopharmacology 22.1 (2014): 35. PMCID: PMC4292872

3. Moore CF, Protzuk OA, Johnson BA, Lynch WJ (2014), The efficacy of a low dose combination of topiramate and naltrexone on ethanol reinforcement and consumption in rat models. Pharmacology Biochemistry and Behavior 116; 107-115. PMCID: PMC3886549

As an undergraduate in Dr. Wendy Lynch’s lab (2010-2012), I made important contributions to studies investigating exercise as a potential therapeutic for nicotine addiction in an adolescent rodent model. Cigarette smoking is the leading cause of preventable death; most smokers initiate use during adolescence, and those that do find it more difficult to quit. However, current pharmacological treatments of nicotine (e.g. nicotine replacement therapy) are controversial for use in adolescence due to ongoing development. Therefore, we investigated exercise as a non-pharmacological intervention for nicotine addiction.

Using an adolescent animal model of intravenous nicotine self-administration, we found that exercise during an abstinence period was effective in reducing subsequent nicotine seeking when compared to a locked wheel (sedentary) condition. Furthermore, we sought to investigate sex differences in nicotine self-administration in this adolescent model, as well as any differential effects of exercise. We found that females self-administered a greater amount of nicotine than males, ran farther and escalated their running, whereas levels of running were lower and stable in males. As expected, we replicated our data showing that access to a running wheel reduced nicotine seeking in males. However in females, we observed reduced nicotine seeking following access to either an unlocked wheel (exercise) or a locked wheel (sedentary), but not in a home-cage only, “no wheel” condition. These evidences suggest the possibility of environmental enrichment effects or effects of an alternate form of exercise (e.g. climbing or hanging on the wheel). In summary, these studies provide evidence that exercise may be an effective smoking cessation aid in this vulnerable population.

For my undergraduate senior thesis, I investigated the hormonal effects of nicotine addiction in this adolescent model through completing estrous cycle characterization for all females in the study described above. I found that female adolescent rats self-administered significantly more nicotine during the proestrus phase of the estrous cycle compared to other phases as well as males. Furthermore, prior studies done by Dr. Lynch found motivation for nicotine was lowest during proestrus, indicating decreased reinforcing effects during this phase. These results implicate ovarian hormones as a mechanism for the enhanced sensitivity in females to the reinforcing properties of nicotine during adolescence.

1. Sanchez VS, Moore CF, Brunzell DH, Lynch WJ (2013), Sex differences in the effects of exercise as an intervention for adolescent-onset nicotine addiction. Psychopharmacology doi: 10.1007/s00213-013-3359-3. PMCID: PMC3969388

2. Sanchez VS, Moore CF, Brunzell DH, Lynch WJ (2013), Effect of wheel-running during abstinence on subsequent nicotine-seeking in rats. Psychopharmacology 227(3) 403-411 PMCID: PMC3656970