Alcoholism is a chronic disorder characterized by repeated episodes of relapse to alcohol consumption. Potential precipitators of relapse include cues paired with past alcohol use. Subsequent exposure to these stimuli could induce a state of alcohol craving that results in reinstatement of alcohol us. The goals of this proposal are to determine the biological bases of how conditioned cues elicit or inhibit drug-seeking. The long- range objectives of this study are to determine the neurocircuits that regulate the modulation of EtOH-seeking by conditioned cues. The overall hypotheses are that there are two distinct systems that integrate environmental cues that promote or inhibit EtOH-seeking, and that each system is comprised of separate neurocircuits and neurotransmitter systems. These hypotheses will be tested primarily using the alcohol- preferring (P) rat, which demonstrates high alcohol drinking behavior and robust EtOH-seeking and relapse behaviors. Proposed experiments will determine the effects of environmental cues (conditioned excitation and conditioned inhibition) on the expression of context-induced seeking. Proposed experiments will determine the neurochemical consequences of exposure to conditioned cues that promote or inhibit EtOH-seeking. In addition, the proposed experiments will identify the neurotransmitter characteristics of neurons activated by presentation of cues that promote or inhibit EtOH-seeking. Further experiments will determine the effects of altering activity at candidate receptors in discrete brai regions on the ability of conditioned cues to alter EtOH- seeking. Understanding the complex factors that underlie EtOH-seeking behaviors and the ability of environmental cues to potentiate or suppress EtOH-seeking will contribute toward the development of therapeutic strategies to reduce 'craving'and alcohol relapse.
The long-range goals of this project are to better understand the biological basis of alcohol craving and how environmental cues can later alter the expression of alcohol craving. Understanding these neurocircuits of drug-seeking will assist in the development of treatment strategies to reduce alcohol drinking and prevent relapse.
|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|
|Deehan Jr, Gerald A; Knight, Christopher P; Waeiss, R Aaron et al. (2016) Peripheral Administration of Ethanol Results in a Correlated Increase in Dopamine and Serotonin Within the Posterior Ventral Tegmental Area. Alcohol Alcohol 51:535-40|
|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|
|Ding, Zheng-Ming; Ingraham, Cynthia M; Rodd, Zachary A et al. (2015) The reinforcing effects of ethanol within the posterior ventral tegmental area depend on dopamine neurotransmission to forebrain cortico-limbic systems. Addict Biol 20:458-68|
|Hauser, S R; Deehan Jr, G A; Dhaher, R et al. (2015) D1 receptors in the nucleus accumbens-shell, but not the core, are involved in mediating ethanol-seeking behavior of alcohol-preferring (P) rats. Neuroscience 295:243-51|
|Wilden, Jessica A; Qing, Kurt Y; Hauser, Sheketha R et al. (2014) Reduced ethanol consumption by alcohol-preferring (P) rats following pharmacological silencing and deep brain stimulation of the nucleus accumbens shell. J Neurosurg 120:997-1005|
|Hauser, Sheketha R; Wilden, Jessica A; Deehan Jr, Gerald A et al. (2014) Cocaine influences alcohol-seeking behavior and relapse drinking in alcohol-preferring (P) rats. Alcohol Clin Exp Res 38:2678-86|
|Hauser, Sheketha R; Deehan Jr, Gerald A; Toalston, Jamie E et al. (2014) Enhanced alcohol-seeking behavior by nicotine in the posterior ventral tegmental area of female alcohol-preferring (P) rats: modulation by serotonin-3 and nicotinic cholinergic receptors. Psychopharmacology (Berl) 231:3745-55|
|Hauser, Sheketha R; Getachew, Bruk; Oster, Scott M et al. (2012) Nicotine modulates alcohol-seeking and relapse by alcohol-preferring (P) rats in a time-dependent manner. Alcohol Clin Exp Res 36:43-54|