title: Adolescent nicotine sensitization and effects of nicotine on accumbal dopamine release in a rodent model of increased dopamine D2 receptor sensitivity.
abstract: Our laboratory has reported neonatal quinpirole (D(2)/D(3) agonist) treatment to rats increases dopamine D(2) receptor sensitivity that persists throughout the animal's lifetime. This model appears to have clinical relevance to schizophrenia, and smoking is common in this population. Male and female Sprague-dawley rats were neonatally treated with quinpirole from postnatal (P) days 1-21. After habituation from P30 to 32, animals were administered saline or nicotine (0.3, 0.5, or 0.7mg/kg free base) every other day from P33 to 49 and locomotor activity was assessed. Generally, animals neonatally treated with quinpirole and administered nicotine during adolescence demonstrated increased behavioral activity and/or sensitization compared to animals neonatally given saline and sensitized to nicotine as well as controls. However, animals neonatally treated with quinpirole and given the 0.7mg/kg dose of nicotine demonstrated elevated activity throughout testing but did not show sensitization, and only mild sex differences were reported. Therefore, microdialysis was performed on male rats sensitized to the 0.5mg/kg dose of nicotine, and results revealed that neonatal quinpirole sensitized dopamine overflow in response to nicotine to 500% above animals neonatally given saline and sensitized to nicotine at peak levels. In addition, neonatal quinpirole increased the accumbal BDNF in response to nicotine compared to all other groups, and nicotine alone also produced significant increases in striatal and accumbal BDNF. This study reveals that neonatal quinpirole enhanced adolescent nicotine sensitization, accumbal dopamine overflow, and BDNF protein in response to nicotine, which may be related to changes in the brain's reward system.
authors.affiliation: Department of Psychology, East Tennessee State University, Department of Psychology, East Tennessee State University, 807 University Parkway, Box 70649, Johnson City, TN 37614, United States.
authors.forename: Marla K
authors.initials: MK
authors.lastname: Perna
authors.forename: Russell W
authors.initials: RW
authors.lastname: Brown
mesh_terms: D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D003216:Conditioning, Operant / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism*; D018491:Dopamine Agonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004563:Electrochemistry; D005260:Female; D006719:Homovanillic Acid / Q000378:metabolism; D008297:Male; D017551:Microdialysis; D009538:Nicotine / Q000008:administration & dosage*; D018722:Nicotinic Agonists / Q000008:administration & dosage*; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism*; D011247:Pregnancy; D019257:Quinpirole / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D012646:Self Administration; D013997:Time Factors
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D018491:Dopamine Agonists; D018722:Nicotinic Agonists; D017448:Receptors, Dopamine D2; D015102:3,4-Dihydroxyphenylacetic Acid; D019257:Quinpirole; D009538:Nicotine; D004298:Dopamine; D006719:Homovanillic Acid