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Impact of adolescent nicotine exposure on adenylyl cyclase-mediated cell signaling: enzyme induction, neurotransmitter-specific effects, regional selectivities, and the role of withdrawal.

Publication ,  Journal Article
Abreu-Villaça, Y; Seidler, FJ; Slotkin, TA
Published in: Brain Res
October 24, 2003

Recent animal studies indicate that the adolescent brain is especially vulnerable to nicotine-induced alterations in synaptic function, echoing the increased susceptibility to nicotine dependence and withdrawal noted for adolescent smokers. We administered nicotine to adolescent rats via continuous minipump infusions from PN30 to PN47.5, using 6 mg/kg/day, a dose rate that replicates the plasma nicotine levels found in smokers, and examined the effects on cell signaling mediated through adenylyl cyclase (AC) and its response to catecholamines. Studies were conducted during nicotine administration (PN45) and in the posttreatment, withdrawal period (PN50, 60, 75). Adolescent nicotine augmented AC activity as evidenced by increased responsiveness to the direct AC stimulants, forskolin and Mn(2+). The effects on AC were equally noted in brain regions enriched (striatum) or sparse (cerebellum) in cholinergic projections, implying that the effects are secondary to activation/repression of neural circuits, rather than representing direct effects on AC mediated by nicotinic cholinergic receptors. AC responses to dopaminergic and noradrenergic stimulants were also enhanced by nicotine exposure. However, in contrast to earlier work with serotonin-mediated responses, the effects on catecholaminergic stimulation were smaller and did not display the sex-dependence noted for serotonin. An alternate administration paradigm that maximizes episodic withdrawal (twice-daily nicotine injections) induced AC more rapidly at lower nicotine doses. Our results indicate that adolescent nicotine exposure elicits lasting alterations in synaptic signaling that intensify and persist during withdrawal. These findings support the concept that the adolescent brain is especially susceptible to persistent nicotine-induced alterations.

Duke Scholars

Published In

Brain Res

DOI

ISSN

0006-8993

Publication Date

October 24, 2003

Volume

988

Issue

1-2

Start / End Page

164 / 172

Location

Netherlands

Related Subject Headings

  • Signal Transduction
  • Rats, Sprague-Dawley
  • Rats
  • Nicotinic Agonists
  • Nicotine
  • Neurology & Neurosurgery
  • Dopamine Agonists
  • Corpus Striatum
  • Cerebellum
  • Catecholamines
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Abreu-Villaça, Y., Seidler, F. J., & Slotkin, T. A. (2003). Impact of adolescent nicotine exposure on adenylyl cyclase-mediated cell signaling: enzyme induction, neurotransmitter-specific effects, regional selectivities, and the role of withdrawal. Brain Res, 988(1–2), 164–172. https://doi.org/10.1016/s0006-8993(03)03368-7
Abreu-Villaça, Yael, Frederic J. Seidler, and Theodore A. Slotkin. “Impact of adolescent nicotine exposure on adenylyl cyclase-mediated cell signaling: enzyme induction, neurotransmitter-specific effects, regional selectivities, and the role of withdrawal.Brain Res 988, no. 1–2 (October 24, 2003): 164–72. https://doi.org/10.1016/s0006-8993(03)03368-7.
Abreu-Villaça, Yael, et al. “Impact of adolescent nicotine exposure on adenylyl cyclase-mediated cell signaling: enzyme induction, neurotransmitter-specific effects, regional selectivities, and the role of withdrawal.Brain Res, vol. 988, no. 1–2, Oct. 2003, pp. 164–72. Pubmed, doi:10.1016/s0006-8993(03)03368-7.
Journal cover image

Published In

Brain Res

DOI

ISSN

0006-8993

Publication Date

October 24, 2003

Volume

988

Issue

1-2

Start / End Page

164 / 172

Location

Netherlands

Related Subject Headings

  • Signal Transduction
  • Rats, Sprague-Dawley
  • Rats
  • Nicotinic Agonists
  • Nicotine
  • Neurology & Neurosurgery
  • Dopamine Agonists
  • Corpus Striatum
  • Cerebellum
  • Catecholamines