The proposed experiments utilize a C5713L/6 (B6) murine model to determine if gender and/or estrus state influence the response to ethanol and ethanol conditioned stimuli or influence the impact of potential therapeutic agents on the response to ethanol-related stimuli. Although both positive and negative reinforcing stimuli regulate behavior directed toward obtaining and consuming ethanol and other abused drugs, we focus on evaluating the influence of gender on the effect on the positive reinforcing stimuli related to ethanol. Such information is basic and applicable to conditions reflective of """"""""craving"""""""", """"""""loss of control"""""""", or """"""""relapse after abstinence"""""""", all of which have ethanol-related stimuli as a component. Although female members of our society contribute to the alcoholic population, preclinical investigations on potential therapeutic agents focus almost exclusively on young male rats. The general hypothesis guiding the proposed research is that gender and estrus state will (1) influence the rewarding effects of ethanol and ethanol -conditioned stimuli and (2) influence the ability of potential therapeutic agents to reduce the reward value of these stimuli. The strategy for testing this hypothesis is to compare the impact of ethanol-related stimuli in male and female mice as well as female mice during two distinct stages of estrus. The effect of estrus cycle on the effect of potential therapeutic agents (Naltrexone, Onclansetron, Vigabatrin) will be measured using behavioral evaluations of the rewarding effects of ethanol and ethanol-conditioned stimuli. Opioid antagonists (Naltrexone) 5-HT3 antagonists (Ondansetron) and GABA transaminase inhibitors (Vigabatrin) have all been shown to attenuate the rewarding effects of ethanol in male monkeys, rats, and mice and can also reduce the rewarding effects of ethanol-conditioned stimuli in male rats and mice. Whether effects on female members of the different species follow those noted for males is unknown, and is the focus of this proposal. An important aspect of the proposed work is to establish whether the drugs can attenuate the rewarding effects of ethanol and ethanol-conditioned stimuli with few unwanted side effects in female mice as we have demonstrated for male mice. Although the experiments are for ethanol reward, they should be generalized to treatment in paradigms for other drugs of abuse such as cocaine, heroin and morphine.
| Moran-Santa Maria, Megan M; Sherman, Brian J; Brady, Kathleen T et al. (2018) Impact of endogenous progesterone on reactivity to yohimbine and cocaine cues in cocaine-dependent women. Pharmacol Biochem Behav 165:63-69 |
| Kohtz, Amy S; Lin, Belle; Smith, Michael E et al. (2018) Attenuated cocaine-seeking after oxytocin administration in male and female rats. Psychopharmacology (Berl) 235:2051-2063 |
| Moran-Santa Maria, Megan M; Vanderweyen, Davy C; Camp, Christopher C et al. (2018) Network Analysis of Intrinsic Functional Brain Connectivity in Male and Female Adult Smokers: A Preliminary Study. Nicotine Tob Res 20:810-818 |
| Sherman, Brian J; Baker, Nathaniel L; Squeglia, Lindsay M et al. (2018) Approach bias modification for cannabis use disorder: A proof-of-principle study. J Subst Abuse Treat 87:16-22 |
| Tomko, Rachel L; Saladin, Michael E; Baker, Nathaniel L et al. (2018) Sex Differences in Subjective and Behavioral Responses to Stressful and Smoking Cues Presented in the Natural Environment of Smokers. Nicotine Tob Res : |
| Moreland, Angela D; McRae-Clark, Aimee (2018) Parenting outcomes of parenting interventions in integrated substance-use treatment programs: A systematic review. J Subst Abuse Treat 89:52-59 |
| Spencer, Sade; Neuhofer, Daniela; Chioma, Vivian C et al. (2018) A Model of ?9-Tetrahydrocannabinol Self-administration and Reinstatement That Alters Synaptic Plasticity in Nucleus Accumbens. Biol Psychiatry 84:601-610 |
| Cox, Brittney M; Bentzley, Brandon S; Regen-Tuero, Helaina et al. (2017) Oxytocin Acts in Nucleus Accumbens to Attenuate Methamphetamine Seeking and Demand. Biol Psychiatry 81:949-958 |
| Melis, Miriam; Frau, Roberto; Kalivas, Peter W et al. (2017) New vistas on cannabis use disorder. Neuropharmacology 124:62-72 |
| Leong, Kah-Chung; Freeman, Linnea R; Berini, Carole R et al. (2017) Oxytocin Reduces Cocaine Cued Fos Activation in a Regionally Specific Manner. Int J Neuropsychopharmacol 20:844-854 |
Showing the most recent 10 out of 106 publications
