Alcoholics go through multiple detoxifications with each episode being more severe and the likelihood of relapse higher with each episode. In addition, cues associated with alcohol drinking can enhance 'craving'and precipitate relapse drinking. The overall goals of this project are to determine neuronal mechanisms underlying cue-induced ethanol (EtOH)-seeking behavior and the effects that repeated deprivation cycles have on these mechanisms. The overall hypothesis is that increased activities of dopamine (DA) and glutamate (Glu) pathways within the meso-cortico-limbic system underlie cue-induced EtOH-seeking behavior and the activities of these pathways are further enhanced with repeated deprivation cycles. A Pavlovian Spontaneous Recovery (PSR) test will be used to measure expression of EtOH-seeking behavior in alcohol-preferring (P) rats following prolonged abstinence. Repeated 2-week cycles of abstinence and operant ethanol access will be used to evaluate the effects of repeated deprivations on cue-induced EtOH-seeking behavior. No-net-flux (NNF) and conventional in vivo microdialysis techniques will be used to examine the involvement of DA, Glu and GABA systems in EtOH-seeking behavior, and changes in these systems associated with distinct cues and repeated deprivations. Microinjection procedures will be used to identify pathways and receptors involved in regulating EtOH-seeking behavior.
Aim 1 will determine the interactions of odor cues and repeated deprivations on expression of EtOH-seeking behavior and transmitter release.
Aim 2 will assess the effects of repeated deprivations on basal neurotransmission of DA, Glu and GABA within the meso-limbic system that persists in the absence of EtOH.
Aim 3 will use microinjection techniques to assess the involvement of different receptors in regulating cue-induced EtOH-seeking behavior. Overall, this project will provide important information on neuronal mechanisms involved in regulating cue-induced EtOH-seeking behavior and the impact of repeated deprivations on these neuronal systems.

Public Health Relevance

Most alcoholics go through multiple periods of abstinence followed by relapse drinking with each relapse episode being more severe than the previous one. Cues associated with alcohol drinking can enhance craving and promote relapse drinking. Understanding brain mechanisms involved in craving and the impact that repeated episodes of abstinence and relapse drinking have on this behavior would help provide a foundation for developing treatment strategies to reduce 'craving'and prevent relapse drinking.

National Institute of Health (NIH)
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Research Project (R01)
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Neurotoxicology and Alcohol Study Section (NAL)
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Grakalic, Ivana
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Indiana University-Purdue University at Indianapolis
Schools of Medicine
United States
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Hauser, Sheketha R; Deehan Jr, Gerald A; Knight, Christopher P et al. (2016) Parameters of Context-Induced Ethanol (EtOH)-Seeking in Alcohol-Preferring (P) Rats: Temporal Analysis, Effects of Repeated Deprivation, and EtOH Priming Injections. Alcohol Clin Exp Res 40:2229-2239
Knight, Christopher P; Hauser, Sheketha R; Deehan Jr, Gerald A et al. (2016) Oral Conditioned Cues Can Enhance or Inhibit Ethanol (EtOH)-Seeking and EtOH-Relapse Drinking by Alcohol-Preferring (P) Rats. Alcohol Clin Exp Res 40:906-15
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