Progressive ratio responding for morphine is differentially altered in the presence of chronic peripheral neuropathy in male vs. female C57Bl/6 mice

Abstract

s / Drug and Alcohol Dependence 146 (2015) e34–e117 e49 prescription opioid of demonstrated abuse potential, the current study was designed to determine if SVA, when contingently administered with the mu agonist, oxycodone, could reduce the reinforcing effectiveness of oxycodone. Methods: Male rhesus monkeys (n=3) were trained to selfadminister cocaine (0.1 or 0.2mg/kg/inj) under a progressive-ratio (PR) schedule of reinforcement with alternating saline sessions. Once self-administration was stable, tests were inserted into the sequence. Test conditions consisted of a range of doses of oxycodone alone (0.006–0.1mg/kg/inj) or oxycodone mixed with a dose of SVA mg/kg/inj). Results: Oxycodone self-administration resulted in biphasic dose response functions, with the highest breakpoint occurring at the 0.05mg/kg dose in all three monkeys. Combining SVA with oxycodone resulted in rightward and downward shifts in the doseresponse functions for oxycodone, indicating a decrease in both the potency and effectiveness of oxycodone as a reinforcer. Conclusions: Our findings demonstrate that SVA, when contingently administered with oxycodone, decreases the reinforcing effectiveness of oxycodone under the current PR schedule conditions. Addingkappa agonists to prescriptionopioidsmaybe a viable abuse-deterrent formulation strategy. Financial support: This research was supported by grants R01DA-027666 to KBF and R01-DA-018151 to TEP from the National Institute on Drug Abuse. http://dx.doi.org/10.1016/j.drugalcdep.2014.09.503 Progressive ratio responding for morphine is differentially altered in the presence of chronic peripheral neuropathy in male vs. female C57Bl/6 mice Harshini Neelakantan, Sara J. Ward, Ellen A. Walker Temple University, Philadelphia, PA, United States Aims: Clinical management of chronic pain with prescription opioids remains a challenge due to concerns about opioid-induced dependence and addiction. Sex-differences in pain sensitivity, opioid analgesia, and reinforcing effects of opioids are observed in rodents. The purpose of our study is to test the hypothesis that the presence of paclitaxel-induced chronic peripheral neuropathy will differentially alter the sensitivities of male and female mice to morphine-induced reinforcing effects. Methods: Male and female C57Bl/6 mice were implanted with indwelling catheters and trained to self-administer morphine under a progressive ratio (PR) schedule of reinforcement. Following stable responding,micewere treatedwith saline or paclitaxel (PAC) and tested formorphine (0.01–0.1mg/kg/inf) responding under PR. Results: PAC treatment produced higher breakpoints for morphine that increased progressively with the development of allodynia in male but not in female mice. A significant upward shift in the dose-effect curve for morphine was observed in the PAC-treated male mice. While only the PAC-treated male mice demonstrated an increase in motivation to respond for morphine, increases in the PR responding for morphine were observed in both in the salineand PAC-treated female groups. The cumulative records from the self-administration sessions displayed marked differences in the pattern of drug-taking behavior in the PAC versus controlmalemice. Further, PAC-treatedmalemicedisplayed increased intake of the prescription opioidmorphine in the state of chronic pain compared to their saline-treated counterparts. Conclusions: The reinforcing effects and the motivational salience of morphine are altered by the presence of paclitaxelinduced peripheral neuropathy with male mice displaying greater sensitivity to these effects compared to female mice. Overall, these results may have implications for the understanding of potential sex differences in the clinical management of pain and the genderdependent abuse liability of prescription opioids in humans. Financial support: Supported by R01 CA129092. http://dx.doi.org/10.1016/j.drugalcdep.2014.09.504 Patterns of crack use among drug-using females in Mexico city Nalini Negi1, Avelardo Valdez2, Alice Cepeda2, Guillermina Natera3 1 School of Social Work, University of Maryland, Baltimore, Baltimore, MD, United States 2 School of Social Work, University of Southern California, Los Angeles, CA, United States 3 Instituto de Psiquiatria, Ramon de la Fuente Muniz,