Ethanol is able to increase neuronal firing in the mesolimbic dopamine pathways associated with drug addiction. Repeated ethanol treatment can change the activity of these neurons and that of other related pathways such that stimuli associated with alcohol use can induce cravings and increase the probability of relapse to drinking. Acamprosate, a calcium homologue of taurine, has been shown to decrease craving and relapse in abstinent alcoholics, suggesting an action on neurotransmitter signaling in these areas. Preliminary data for the proposed experiments indicates that both injected and self-administered ethanol increase dopamine and taurine levels in the nucleus accumbens (Nac), the terminal area of the mesolimbic pathway. Interestingly, only self-administered ethanol (not injected ethanol) consistently results in an increase in glutamate release in Nac. We hypothesize that alterations in ethanol-induced increases in taurine levels in Nac may be a media in ism for inducing persistent alcohol cravings via an interaction with dopamine and glutamate efflux. This proposal describes a series of experiments that will characterize the mechanism for the ethanol-induced efflux of glutamate, taurine and dopamine in Nac and other limbic regions as well as determine the relationship between these neurotransmitters and changes in the """"""""non-transmitter"""""""" amino acid environment caused by ethanol. Comparing the effect of a low dose of injected ethanol in na'ive and ethanoltrained rats will allow distinction of alterations in these relationships by the induction of self-administration (the first step in the process of alcohol addiction) as well as progression to more alcoholic-like behaviors. Using capillary electrophoresis coupled with laser-induced fluorescence detection, the effects of low doses of ethanol on the levels of at least 10 amino acids plus dopamine in brain regions important for mediating ethanol self-administration (Nac, central nucleus of the amygdala) and striatum as a control region, will be measured. The very high time resolution (in seconds) provided by this methodology will allow us to distinguish changes in neurotransmitter levels during anticipation of ethanol versus that caused pharmacologically by consuming ethanol. Since the anticipation of ethanol is a likely component of craving and relapse to alcohol, this approach will provide new information about the involvement of changes in neurotransmitter release in alcohol relapse so that more effective strategies can be developed for the successful treatment of ethanol abuse.
| MacFadyen, Kaley; Loveless, Rebecca; DeLucca, Brandon et al. (2016) Peripheral oxytocin administration reduces ethanol consumption in rats. Pharmacol Biochem Behav 140:27-32 |
| Peris, Joanna; Rhodes, Nathaniel; McCullough, Brian et al. (2015) Intermittent high-dose ethanol exposure increases ethanol preference in rats. J Stud Alcohol Drugs 76:165-73 |
| Li, Zhimin; Zharikova, Alevtina; Vaughan, Cheryl H et al. (2010) Intermittent high-dose ethanol exposures increase motivation for operant ethanol self-administration: possible neurochemical mechanism. Brain Res 1310:142-53 |
| Li, Zhimin; Zharikova, Aleutina; Bastian, Jaime et al. (2008) High temporal resolution of amino acid levels in rat nucleus accumbens during operant ethanol self-administration: involvement of elevated glycine in anticipation. J Neurochem 106:170-81 |
| Peris, J; Zharikova, A; Li, Z et al. (2006) Brain ethanol levels in rats after voluntary ethanol consumption using a sweetened gelatin vehicle. Pharmacol Biochem Behav 85:562-8 |
