title: Nicotine modulation of adolescent dopamine receptor signaling and hypothalamic peptide response.
abstract: Adolescence is a sensitive developmental period for limbic and dopamine systems that coincides with the typical age for onset of tobacco use. We have previously shown that a 4-day, low-dose nicotine (0.06 mg/kg) pretreatment enhances locomotor and penile response to the D2-like agonist, quinpirole (0.4 mg/kg), in adolescent but not adult rats. The present study is designed to determine mechanisms underlying this effect. Nicotine enhancement of adolescent quinpirole-induced locomotion was mediated by D2 receptors (D2Rs) since it was blocked by the D2R antagonist, L-741,626, but not by the D3R and D4R antagonists, NGB 2904 and L-745,870. Enhancement of quinpirole-induced erectile response was blocked by both L-741,626 and NGB 2904, indicating involvement of D3Rs. Whereas D2R binding was unaffected by adolescent nicotine pretreatment, effector coupling in the striatum was increased, as determined by GTPγS binding. Nicotine pretreatment enhanced quinpirole-induced c-fos mRNA expression in the hypothalamic paraventricular and supraoptic nuclei in adolescents only. Adolescent nicotine pretreatment enhanced c-fos mRNA expression in corticotropin releasing factor (CRF) cells of the paraventricular nucleus, and enhancement of penile erection was blocked by the CRF-1 receptor antagonist, CP 376,396. These findings suggest that adolescent dopamine and CRF systems are vulnerable to alteration by nicotine. This is the first evidence for a role of CRF in adolescent erectile response.
authors.affiliation: Department of Pharmacology, School of Medicine, University of California, Irvine, CA 92697-4625, USA. Electronic address: cmojica@uci.edu.
authors.forename: Celina Y
authors.initials: CY
authors.lastname: Mojica
authors.affiliation: Department of Anatomy & Neurobiology, School of Medicine, University of California, Irvine, CA 92697-4625, USA.
authors.forename: Jasmin M
authors.initials: JM
authors.lastname: Dao
authors.affiliation: Department of Pharmacology, School of Medicine, University of California, Irvine, CA 92697-4625, USA.
authors.forename: Menglu
authors.initials: M
authors.lastname: Yuan
authors.affiliation: Department of Pharmacology, School of Medicine, University of California, Irvine, CA 92697-4625, USA.
authors.forename: Sandra E
authors.initials: SE
authors.lastname: Loughlin
authors.affiliation: Department of Pharmacology, School of Medicine, University of California, Irvine, CA 92697-4625, USA; Department of Anatomy & Neurobiology, School of Medicine, University of California, Irvine, CA 92697-4625, USA.
authors.forename: Frances M
authors.initials: FM
authors.lastname: Leslie
mesh_terms: D000818:Animals; D018491:Dopamine Agonists / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009538:Nicotine / Q000494:pharmacology*; D010410:Penile Erection / Q000187:drug effects; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D019257:Quinpirole / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000378:metabolism*
chemical_list: D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D016760:Proto-Oncogene Proteins c-fos; D017448:Receptors, Dopamine D2; D019257:Quinpirole; D009538:Nicotine
keywords: Corticotropin releasing factor; Locomotion; Oxytocin; Paraventricular nucleus; Penile erection; Tobacco