Neuropsychopharmacology (New York, N.Y.), 2011-06, Vol.36 (7), p.1319-1331
2011
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- Autor(en) / Beteiligte
- Titel
- Nicotine Alters Limbic Function in Adolescent Rat by a 5-HT1A Receptor Mechanism
- Ist Teil von
- Neuropsychopharmacology (New York, N.Y.), 2011-06, Vol.36 (7), p.1319-1331
- Ort / Verlag
- England: Nature Publishing Group
- Erscheinungsjahr
- 2011
- Quelle
- Free E-Journal (出版社公開部分のみ）
- Beschreibungen/Notizen
- Epidemiological studies have shown that adolescent smoking is associated with health risk behaviors, including high-risk sexual activity and illicit drug use. Using rat as an animal model, we evaluated the behavioral and biochemical effects of a 4-day, low-dose nicotine pretreatment (60 μg/kg; intravenous) during adolescence and adulthood. Nicotine pretreatment significantly increased initial acquisition of cocaine self-administration, quinpirole-induced locomotor activity, and penile erection in adolescent rats, aged postnatal day (P)32. These effects were long lasting, remaining evident 10 days after the last nicotine treatment, and were observed when nicotine pretreatment was administered during early adolescence (P28-31), but not late adolescence (P38-41) or adulthood (P86-89). Neurochemical analyses of c-fos mRNA expression, and of monoamine transmitter and transporter levels, showed that forebrain limbic systems are continuing to develop during early adolescence, and that this maturation is critically altered by brief nicotine exposure. Nicotine selectively increased c-fos mRNA expression in the nucleus accumbens shell and basolateral amygdala in adolescent, but not adult animals, and altered serotonin markers in these regions as well as the prefrontal cortex. Nicotine enhancement of cocaine self-administration and quinpirole-induced locomotor activity was blocked by co-administration of WAY 100 635 (N-{2-[4-(2-methoxyphenyl)-1-piperazinyl] ethyl}-N-(2-pyridinyl)cyclohexanecarboxamide), a selective serotonin 1A (5-HT1A) receptor antagonist. Early adolescent pretreatment with the mixed autoreceptor/heteroceptor 5-HT1A receptor agonist, 8-OH-DPAT, but not the autoreceptor-selective agonist, S-15535, also enhanced quinpirole-induced locomotor activation. Nicotine enhancement of quinpirole-induced penile erection was not blocked by WAY 100 635 nor mimicked by 8-OH-DPAT. These findings indicate that early adolescent nicotine exposure uniquely alters limbic function by both 5-HT1A and non-5-HT1A receptor mechanisms.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0893-133XeISSN: 1740-634XDOI: 10.1038/npp.2011.8Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3096821
- Format
- –
- Schlagworte
- 3,4-Dihydroxyphenylacetic Acid - metabolism, 8-Hydroxy-2-(di-n-propylamino)tetralin - pharmacology, Addictive behaviors, Adults, Age Factors, Analysis of Variance, Animals, Animals, Newborn, Attention deficit hyperactivity disorder, Autoradiography - methods, Behavior, Catecholamines - metabolism, Child development, Cocaine, Dopamine, Dopamine Agonists - pharmacology, Drug abuse, Drug Administration Schedule, Drug dosages, Drug Interactions, Drug use, Emotional disorders, Gene Expression Regulation - drug effects, Health risk assessment, Health risks, Limbic System - drug effects, Locomotion - drug effects, Male, Mood disorders, Neurobiology, Neurosciences, Nicotine, Nicotine - pharmacology, Nicotinic Agonists - pharmacology, Original, Penis, Piperazines - pharmacology, Protein Binding - drug effects, Quinpirole - pharmacology, Rats, Rats, Sprague-Dawley, Receptor, Serotonin, 5-HT1A - genetics, Receptor, Serotonin, 5-HT1A - metabolism, Reward, RNA, Messenger - metabolism, Self Administration - methods, Serotonin, Serotonin Plasma Membrane Transport Proteins - genetics, Serotonin Plasma Membrane Transport Proteins - metabolism, Serotonin Receptor Agonists - pharmacology, Smoking, Teenagers, Time Factors