An analysis of the rewarding and aversive associative properties of nicotine in the neonatal quinpirole model: Effects on glial cell line-derived neurotrophic factor (GDNF).
This study analyzed the associative properties of nicotine in a conditioned place preference (CPP) paradigm in adolescent rats neonatally treated with quinpirole (NQ) or saline (NS). NQ produces dopamine D2receptor supersensitivity that persists throughout the animal's lifetime, and therefore has relevance towards schizophrenia. In two experiments, rats were ip administered quinpirole (1mg/kg) or saline from postnatal day (P)1-21. After an initial preference test at P42-43, animals were conditioned for eight consecutive days with saline or nicotine (0.6mg/kg free base) in Experiment 1 or saline or nicotine (1.8mg/kg free base) in Experiment 2. In addition, there were NQ and NS groups in each experiment given the antipsychotic haloperidol (0.05mg/kg) or clozapine (2.5mg/kg) before nicotine conditioning. A drug free post-conditioning test was administered at P52. At P53, the nucleus accumbens (NAc) was analyzed for glial cell-line derived neurotrophic factor (GDNF). Results revealed that NQ enhanced nicotine CPP, but blunted the aversive properties of nicotine. Haloperidol was more effective than clozapine at blocking nicotine CPP in Experiment 1, but neither antipsychotic affected nicotine conditioned place aversion in Experiment 2. NQ increased accumbal GDNF which was sensitized in NQ rats conditioned to nicotine in Experiment 1, but the aversive dose of nicotine reduced GDNF in NQ animals in Experiment 2. Both antipsychotics in combination with the aversive dose of nicotine decreased accumbal GDNF. In sum, increased D2receptor sensitivity influenced the associative properties and GDNF response to nicotine which has implications towards pharmacological targets for smoking cessation in schizophrenia.
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.
Russell W
RW
Brown
Department of Psychology, East Tennessee State University, Johnson City, TN 37614, United States.
Seth L
SL
Kirby
Department of Psychology, East Tennessee State University, Johnson City, TN 37614, United States.
Adam R
AR
Denton
Department of Psychology, St. Norbert College, De Pere, WI 54115, United States.
John M
JM
Dose
Department of Psychology, East Tennessee State University, Johnson City, TN 37614, United States.
Elizabeth D
ED
Cummins
Department of Biomedical Sciences, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, United States.
Wesley
W
Drew Gill
Department of Biomedical Sciences, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, United States.
Katherine C
KC
Burgess
D000818:Animals; D000831:Animals, Newborn; D014150:Antipsychotic Agents / Q000494:pharmacology; D001244:Association; D001362:Avoidance Learning / Q000187:drug effects*; D003024:Clozapine / Q000494:pharmacology; D003213:Conditioning, Psychological / Q000187:drug effects / Q000502:physiology; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000378:metabolism*; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D009538:Nicotine / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000494:pharmacology; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D019257:Quinpirole; D012201:Reward; D013037:Spatial Behavior / Q000187:drug effects / Q000502:physiology; D014029:Tobacco Use Disorder / Q000378:metabolism* / Q000473:pathology / Q000523:psychology*
D014150:Antipsychotic Agents; C495041:Gdnf protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D018722:Nicotinic Agonists; D019257:Quinpirole; D009538:Nicotine; D003024:Clozapine; D006220:Haloperidol
Adolescence; Antipsychotics; Conditioned place preference; Dopamine D2 receptor; Nicotine; Schizophrenia