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

• Published in: Psychopharmacology 2015-12, Vol.232 (23), p.4293-4302
• Main Authors: Deehan, Gerald A., Hauser, Sheketha R., Waeiss, R. Aaron, Knight, Christopher P., Toalston, Jamie E., Truitt, William A., McBride, William J., Rodd, Zachary A.
• Format: Article
• Language: English
• Subjects: Alcohol Drinking - metabolism; Alcohol Drinking - psychology; Alcohol use; Alcoholism; Alcoholism - metabolism; Alcoholism - psychology; Animals; Biomedical and Life Sciences; Biomedicine; Drug Combinations; Ethanol; Ethanol - administration & dosage; Female; Glutamic Acid - metabolism; Health aspects; Limbic system; Limbic System - drug effects; Limbic System - metabolism; Neurosciences; Nicotine; Nicotine - administration & dosage; Nucleus Accumbens - drug effects; Nucleus Accumbens - metabolism; Original Investigation; Pharmacology/Toxicology; Psychiatry; Psychopharmacology; Rats; Reward; Rewards (Psychology); Rodents; Self Administration; Smoking; Tobacco habit
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/s00213-015-4056-1

Rationale 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. Objectives 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.