AN EXAMINATION OF DEVELOPMENTAL AND SEX DIFFERENCES IN ETHANOL CONSUMPTION BY LOW ALCOHOL-CONSUMING RAT LINES

poster abstractIn the United States, alcohol use and dependence is a major health issue affecting 4-5% of the population (Hasin et al., 2007). Research indicates ad-olescents ages 12-20 drink 11% of all alcohol consumed nationally, with more than 90% consumed in the form of binge drinking (Center for Disease Control and Prevention, 2010). Similar to the human condition, adolescent rodents generally consume more ethanol than their adult counterparts. Current rat animal model studies on alcoholism remain weighted toward examining Family History Positive (FHP), selectively bred, alcohol-preferring lines. Also, research has generally been focused on ethanol consumption be-havior of male rodents. However, female rodents tend to consume more al-cohol than male rodents (e.g., Adams et al., 1991). In addition, existing re-search on adolescent vs. adult alcohol abuse using “FHP” rats is not paral-leled by research with “Family History Negative” (FHN) rats, which might re-veal factors that prevent/protect an individual from excessive ethanol intake during this crucial stage of development. The purpose of this study was to evaluate ethanol consumption by male and female FHN, selectively bred, alcohol-nonpreferring rats during adoles-cence and adulthood. Studying adolescent vs. adult behavior may reveal de-velopmentally-specific, protective factors. Also, examining male versus fe-male behavior may reveal sex-by-development factors guarding against al-cohol abuse. Animals were placed in cages and assigned to experimental conditions defined by the following independent variables: line of rodent, rodent’s sex and age of ethanol exposure. The following dependent measures were exam-ined: changes in body weight as well as water and ethanol consumption. These measures were taken at least 5 days per week. We hypothesized that there would be elevated levels of ethanol con-sumption (g ethanol/kg body weight/day) in (a) adolescent vs. adult rats and (b) female vs. male rats. Future research might focus on gene and/or protein expression differences within certain nuclei of the brain’s reward neurocircuit between the FHP and FHN lines of rats. Currently, some data has been collected and statistically analyzed. Upon completion the study re-sults will be prepared for presentation and manuscript submission. Funded in part by the Indiana University-Purdue University Indianapolis, Undergraduate Re-search Opportunities Program (UROP

The Reinforcing Properties of Drugs of Abuse are Attenuated by Naltrexone in Caenorhabditis elegans

poster abstractDrug addiction is a chronic, relapsing disease premised on compulsive drug seeking. Previous work from our lab demonstrated that the nematode Caenorhabditis elegans (C. elegans) can be used to examine the reinforcing properties of drugs of abuse. A successful model for studying the reinforcing effects of drugs in C. elegans would greatly aid efforts to discover potential therapeutic interventions for drug addiction. The present study examined preference for morphine, ethanol, cocaine, and a cannabinoid agonist (CB agonist) in C. elegans and the effect of naltrexone, an opioid antagonist, on this behavior. Six-well agar test plates were utilized to test drug preference. Each well had two circular target zones equidistant from the center; 4μl of the targeted drug or water were placed in the center of one of the two target zones within each well. Worms in one group were pre-treated with 10mM naltrexone, while controls were pre-treated with 0.97 mM HCl for 30 min prior to testing. Worms in each treatment group were then placed in the center of each well and allowed to move freely for 30 minutes-images were captured at 10 and 30 minutes. Animals treated with vehicle displayed a significant preference for the aforementioned drugs relative to controls; naltrexone pretreatment significantly ameliorated this effect. Naltrexone had no effect on food or chemoatractant preference, indicating that the effects of naltrexone on drug preference are selective and not due to disruption in general behaviors. These findings suggest that the reinforcing properties of drugs of abuse can be examined in C. elegans and this model may be useful for screening potential pharmacotherapies for drug abuse

Caenorhabditis elegans as a model system to identify therapeutics for alcohol use disorders

Alcohol use disorders (AUDs) cause serious problems in society and few effective treatments are available. Caenorhabditis elegans (C. elegans) is an excellent invertebrate model to study the neurobiological basis of human behavior with a conserved, fully tractable genome, and a short generation time for fast generation of data at a fraction of the cost of other organisms. C. elegans demonstrate movement toward, and concentration-dependent self-exposure to various psychoactive drugs. The discovery of opioid receptors in C. elegans provided the impetus to test the hypothesis that C. elegans may be used as a medications screen to identify new AUD treatments. We tested the effects of naltrexone, an opioid antagonist and effective treatment for AUDs, on EtOH preference in C. elegans. Six-well agar test plates were prepared with EtOH placed in a target zone on one side and water in the opposite target zone of each well. Worms were treated with naltrexone before EtOH preference testing and then placed in the center of each well. Wild-type worms exhibited a concentration-dependent preference for 50, 70 and 95% EtOH. Naltrexone blocked acute EtOH preference, but had no effect on attraction to food or benzaldehyde in wild-type worms. Npr-17 opioid receptor knockout mutants did not display a preference for EtOH. In contrast, npr-17 opioid receptor rescue mutants exhibited significant EtOH preference behavior, which was attenuated by naltrexone. Chronic EtOH exposure induced treatment resistance and compulsive-like behavior. These data indicate that C. elegans can serve as a model system to identify compounds to treat AUDs

Caenorhabditis elegans Show Preference for Stimulants and Potential as a Model Organism for Medications Screening

The nematode Caenorhabditis elegans (C. elegans) is a popular invertebrate model organism to study neurobiological disease states. This is due in part to the intricate mapping of all neurons and synapses of the entire animal, the wide availability of mutant strains, and the genetic and molecular tools that can be used to manipulate the genome and gene expression. We have shown that, C. elegans develops a conditioned preference for cues that had previously been paired with either cocaine or methamphetamine exposure that is dependent on dopamine neurotransmission, similar to findings using place conditioning with rats and mice. In the current study, we show C. elegans also display a preference for, and self-exposure to, cocaine and nicotine. This substance of abuse (SOA) preference response can be selectively blocked by pretreatment with naltrexone and is consistent with the recent discovery of an opioid receptor system in C. elegans. In addition, pre-exposure to the smoking cessation treatment varenicline also inhibits self-exposure to nicotine. Exposure to concentrations of treatments that inhibit SOA preference/self-exposure did not induce any significant inhibition of locomotor activity or affect food or benzaldehyde chemotaxis. These data provide predictive validity for the development of high-throughput C. elegans behavioral medication screens. These screens could enable fast and accurate generation of data to identify compounds that may be effective in treating human addiction. The successful development and validation of such models would introduce powerful and novel tools in the search for new pharmacological treatments for substance use disorders, and provide a platform to study the mechanisms that underlie addictions