title: A key role for the N/OFQ-NOP receptor system in modulating nicotine taking in a model of nicotine and alcohol co-administration.
abstract: Alcohol and nicotine are often co-abused. Although the N/OFQ-NOP receptor system is considered a potential target for development of drug abuse pharmacotherapies, especially for alcoholism, little is known about the role of this system in nicotine dependence. Furthermore, the effect of prior history of nicotine dependence on subsequent nicotine and alcohol taking is understudied. Using an operant co-administration paradigm, in which rats concurrently self-administer nicotine and alcohol, we found that nicotine dependent rats increased nicotine self-administration over time as compared to non-dependent animals, while patterns of alcohol lever pressing did not change between groups. Pretreatment with the potent NOP receptor agonist AT-202 (0.3-3 mg/kg) increased nicotine lever pressing of both dependent and non-dependent groups, whereas the selective antagonist SB612111 (1-10 mg/kg) elicited a clear reduction of nicotine responses, in both dependent and non-dependent rats. In parallel, AT-202 only produced minor changes on alcohol responses and SB612111 reduced alcohol taking at a dose that also reduced locomotor behavior. Results indicate that a history of nicotine dependence affects subsequent nicotine- but not alcohol-maintained responding, and that NOP receptor antagonism, rather than agonism, blocks nicotine self-administration, which strongly suggests a critical role for the endogenous N/OFQ in the modulation of nicotine reinforcement processes.
authors.affiliation: Torrey Pines Institute for Molecular Studies, 11350 SW Village Parkway, Port St. Lucie, FL 34987, USA.
authors.forename: Andrea
authors.initials: A
authors.lastname: Cippitelli
authors.affiliation: Torrey Pines Institute for Molecular Studies, 11350 SW Village Parkway, Port St. Lucie, FL 34987, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Schoch
authors.affiliation: Torrey Pines Institute for Molecular Studies, 11350 SW Village Parkway, Port St. Lucie, FL 34987, USA.
authors.forename: Ginamarie
authors.initials: G
authors.lastname: Debevec
authors.affiliation: Torrey Pines Institute for Molecular Studies, 11350 SW Village Parkway, Port St. Lucie, FL 34987, USA.
authors.forename: Gloria
authors.initials: G
authors.lastname: Brunori
authors.affiliation: Astraea Therapeutics, 320 Logue Avenue, Suite 142, Mountain View, CA 94043, USA.
authors.forename: Nurulain T
authors.initials: NT
authors.lastname: Zaveri
authors.affiliation: Torrey Pines Institute for Molecular Studies, 11350 SW Village Parkway, Port St. Lucie, FL 34987, USA.
authors.forename: Lawrence
authors.initials: L
authors.lastname: Toll
mesh_terms: D000437:Alcoholism / Q000378:metabolism*; D000818:Animals; D003216:Conditioning, Operant; D004195:Disease Models, Animal; D058999:Drug-Seeking Behavior; D008297:Male; D009292:Narcotic Antagonists / Q000008:administration & dosage* / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000008:administration & dosage* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011957:Receptors, Opioid / Q000378:metabolism*; D012054:Reinforcement, Psychology; D012646:Self Administration; D014029:Tobacco Use Disorder / Q000378:metabolism* / Q000517:prevention & control; D000094942:Nociceptin Receptor
chemical_list: D009292:Narcotic Antagonists; D018722:Nicotinic Agonists; D011957:Receptors, Opioid; D000094942:Nociceptin Receptor; C000722285:Oprl1 protein, rat