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Neuropharmacology. 2014 Feb;77:285-93. doi: 10.1016/j.neuropharm.2013.10.012. Epub 2013 Oct 22.

Nicotine modulation of adolescent dopamine receptor signaling and hypothalamic peptide response.

Author information

  • 1Department of Pharmacology, School of Medicine, University of California, Irvine, CA 92697-4625, USA. Electronic address: cmojica@uci.edu.
  • 2Department of Anatomy & Neurobiology, School of Medicine, University of California, Irvine, CA 92697-4625, USA.
  • 3Department of Pharmacology, School of Medicine, University of California, Irvine, CA 92697-4625, USA.
  • 4Department 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.

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.

Copyright © 2013 Elsevier Ltd. All rights reserved.

KEYWORDS:

Corticotropin releasing factor; Locomotion; Oxytocin; Paraventricular nucleus; Penile erection; Tobacco

PMID:
24157491
[PubMed - indexed for MEDLINE]
PMCID:
PMC3894780
Free PMC Article
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