title: The effects of nicotine in the neonatal quinpirole rodent model of psychosis: Neural plasticity mechanisms and nicotinic receptor changes.
abstract: Neonatal quinpirole (NQ) treatment to rats increases dopamine D2 receptor sensitivity persistent throughout the animal's lifetime. In Experiment 1, we analyzed the role of α7 and α4β2 nicotinic receptors (nAChRs) in nicotine behavioral sensitization and on the brain-derived neurotrophic factor (BDNF) response to nicotine in NQ- and neonatally saline (NS)-treated rats. In Experiment 2, we analyzed changes in α7 and α4β2 nAChR density in the nucleus accumbens (NAcc) and dorsal striatum in NQ and NS animals sensitized to nicotine. Male and female Sprague-Dawley rats were neonatally treated with quinpirole (1mg/kg) or saline from postnatal days (P)1-21. Animals were given ip injections of either saline or nicotine (0.5mg/kg free base) every second day from P33 to P49 and tested on behavioral sensitization. Before each injection, animals were ip administered the α7 nAChR antagonist methyllycaconitine (MLA; 2 or 4mg/kg) or the α4β2 nAChR antagonist dihydro beta erythroidine (DhβE; 1 or 3mg/kg). Results revealed NQ enhanced nicotine sensitization that was blocked by DhβE. MLA blocked the enhanced nicotine sensitization in NQ animals, but did not block nicotine sensitization. NQ enhanced the NAcc BDNF response to nicotine which was blocked by both antagonists. In Experiment 2, NQ enhanced nicotine sensitization and enhanced α4β2, but not α7, nAChR upregulation in the NAcc. These results suggest a relationship between accumbal BDNF and α4β2 nAChRs and their role in the behavioral response to nicotine in the NQ model which has relevance to schizophrenia, a behavioral disorder with high rates of tobacco smoking.
authors.affiliation: Department of Psychology, East Tennessee State University, Johnson City, TN 37614, United States.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Peterson
authors.affiliation: Department of Biomedical Sciences, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, United States.
authors.forename: W Drew
authors.initials: WD
authors.lastname: Gill
authors.affiliation: Department of Psychology, St. Norbert College, De Pere, WI, 54115,United States.
authors.forename: John M
authors.initials: JM
authors.lastname: Dose
authors.affiliation: Department of Biomedical Sciences, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, United States.
authors.forename: Donald B
authors.initials: DB
authors.lastname: Hoover
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536, United States.
authors.forename: James R
authors.initials: JR
authors.lastname: Pauly
authors.affiliation: Department of Psychology, East Tennessee State University, Johnson City, TN 37614, United States.
authors.forename: Elizabeth D
authors.initials: ED
authors.lastname: Cummins
authors.affiliation: Department of Biomedical Sciences, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, United States.
authors.forename: Katherine C
authors.initials: KC
authors.lastname: Burgess
authors.affiliation: Department of Biomedical Sciences, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, United States. Electronic address: brown1@etsu.edu.
authors.forename: Russell W
authors.initials: RW
authors.lastname: Brown
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009473:Neuronal Plasticity / Q000187:drug effects*; D009538:Nicotine / Q000008:administration & dosage*; D018722:Nicotinic Agonists / Q000008:administration & dosage*; D009714:Nucleus Accumbens / Q000378:metabolism; D011618:Psychotic Disorders / Q000378:metabolism*; D019257:Quinpirole / Q000008:administration & dosage*; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000378:metabolism*; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000378:metabolism*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D018722:Nicotinic Agonists; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; C403531:nicotinic receptor alpha4beta2; D019257:Quinpirole; D009538:Nicotine
keywords: Adolescence; Brain-derived neurotrophic factor (BDNF); Dopamine D2 receptor; Nicotine sensitization; α4β2 nicotinic receptor; α7 nicotinic receptor