title: Co-administration of ethanol and nicotine: the enduring alterations in the rewarding properties of nicotine and glutamate activity within the mesocorticolimbic system of female alcohol-preferring (P) rats.
abstract: BACKGROUND
  The co-abuse of ethanol (EtOH) and nicotine (NIC) increases the likelihood that an individual will relapse to drug use while attempting to maintain abstinence. There is limited research examining the consequences of long-term EtOH and NIC co-abuse.
  
  
  OBJECTIVE
  The current experiments determined the enduring effects of chronic EtOH, NIC, or EtOH + NIC intake on the reinforcing properties of NIC and glutamate (GLU) activity within the mesocorticolimbic (MCL) system.
  
  
  METHODS
  Alcohol-preferring (P) rats self-administered EtOH, Sacc + NIC, or EtOH + NIC combined for 10 weeks. The reinforcing properties of 0.1-3.0 μM NIC within the nucleus accumbens shell (AcbSh) were assessed following a 2-3-week drug-free period using intracranial self-administration (ICSA) procedures. The effects of EtOH, Sacc, Sacc + NIC, or EtOH + NIC intake on extracellular levels and clearance of glutamate (GLU) in the medial prefrontal cortex (mPFC) were also determined.
  
  
  RESULTS
  Binge intake of EtOH (96-100 mg%) and NIC (21-27 mg/mL) were attained. All groups of P rats self-infused 3.0 μM NIC directly into the AcbSh, whereas only animals in the EtOH + NIC co-abuse group self-infused the 0.3 and 1.0 μM NIC concentrations. Additionally, self-administration of EtOH + NIC, but not EtOH, Sacc or Sacc + NIC, resulted in enduring increases in basal extracellular GLU levels in the mPFC.
  
  
  CONCLUSIONS
  Overall, the co-abuse of EtOH + NIC produced enduring neuronal alterations within the MCL which enhanced the rewarding properties of NIC in the AcbSh and elevated extracellular GLU levels within the mPFC.
authors: Department of Psychiatry, Institute of Psychiatric Research, Indiana University School of Medicine, Neuroscience Research Building, 320 West 15th St, Indianapolis, IN, 46202-2266, USA. gdeehan@iupui.edu.
authors: Gerald A
authors: GA
authors: Deehan
authors: Department of Psychiatry, Institute of Psychiatric Research, Indiana University School of Medicine, Neuroscience Research Building, 320 West 15th St, Indianapolis, IN, 46202-2266, USA.
authors: Sheketha R
authors: SR
authors: Hauser
authors: Department of Psychiatry, Institute of Psychiatric Research, Indiana University School of Medicine, Neuroscience Research Building, 320 West 15th St, Indianapolis, IN, 46202-2266, USA.
authors: R Aaron
authors: RA
authors: Waeiss
authors: Department of Psychiatry, Institute of Psychiatric Research, Indiana University School of Medicine, Neuroscience Research Building, 320 West 15th St, Indianapolis, IN, 46202-2266, USA.
authors: Christopher P
authors: CP
authors: Knight
authors: Department of Psychiatry, Institute of Psychiatric Research, Indiana University School of Medicine, Neuroscience Research Building, 320 West 15th St, Indianapolis, IN, 46202-2266, USA.
authors: Jamie E
authors: JE
authors: Toalston
authors: Department of Psychiatry, Institute of Psychiatric Research, Indiana University School of Medicine, Neuroscience Research Building, 320 West 15th St, Indianapolis, IN, 46202-2266, USA.
authors: William A
authors: WA
authors: Truitt
authors: Department of Psychiatry, Institute of Psychiatric Research, Indiana University School of Medicine, Neuroscience Research Building, 320 West 15th St, Indianapolis, IN, 46202-2266, USA.
authors: William J
authors: WJ
authors: McBride
authors: Department of Psychiatry, Institute of Psychiatric Research, Indiana University School of Medicine, Neuroscience Research Building, 320 West 15th St, Indianapolis, IN, 46202-2266, USA.
authors: Zachary A
authors: ZA
authors: Rodd
mesh_terms: D000428:Alcohol Drinking / Q000378:metabolism* / Q000523:psychology; D000437:Alcoholism / Q000378:metabolism / Q000523:psychology; D000818:Animals; D004338:Drug Combinations; D000431:Ethanol / Q000008:administration & dosage*; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism*; D008032:Limbic System / Q000187:drug effects / Q000378:metabolism; D009538:Nicotine / Q000008:administration & dosage*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D012201:Reward; D012646:Self Administration
chemical_list: D004338:Drug Combinations; D000431:Ethanol; D018698:Glutamic Acid; D009538:Nicotine
keywords: Alcohol; Co-abuse; Intracranial self-administration; Medial prefrontal cortex; Nicotine; Nucleus accumbens