Nicotine effects in adolescence and adulthood on cognition and α4β2-nicotinic receptors in the neonatal ventral hippocampal lesion rat model of schizophrenia

Sarah A. Berg, Alena M. Sentir, Richard Bell, Eric Engleman, R. Chambers

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Rational: Nicotine use in schizophrenia has traditionally been explained as "self-medication" of cognitive and/or nicotinic acetylcholinergic receptor (nAChR) abnormalities. Objectives: We test this hypothesis in a neurodevelopmental rat model of schizophrenia that shows increased addiction behaviors including enhanced nicotine reinforcement and drug-seeking. Methods: Nicotine transdermal patch (5 mg/kg/day vs. placebo∈×∈10 days in adolescence or adulthood) effects on subsequent radial-arm maze learning (15 sessions) and frontal-cortical-striatal nAChR densities (α4β2; [3H]-epibatidine binding) were examined in neonatal ventral hippocampal lesion (NVHL) and SHAM-operated rats. Results: NVHL cognitive deficits were not differentially affected by nicotine history compared to SHAMs. Nicotine history produced minimal cognitive effects while increasing food-reward consumption on the maze, compounding with NVHL-induced overconsumption. Acute nicotine (0.5 mg/kg) delivered before the final maze sessions produced modest improvements in maze performance in rats with nicotine patch histories only, but not differentially so in NVHLs. Consistent with in vivo neuroimaging of β2 nAChR binding in schizophrenia smokers vs. non-smokers and healthy controls, adult NVHLs showed 12% reductions in nAChR binding in MPFC (p∈∈.40), whereas nicotine history elevated nAChRs across both regions (>30%, p∈

Original languageEnglish (US)
Pages (from-to)1681-1692
Number of pages12
JournalPsychopharmacology
Volume232
Issue number10
DOIs
StatePublished - May 1 2015

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Nicotinic Receptors
Nicotine
Cognition
Schizophrenia
Tobacco Use Cessation Products
epibatidine
History
Maze Learning
Corpus Striatum
Self Medication
Reward
Neuroimaging
Food
Pharmaceutical Preparations

Keywords

  • Addiction
  • Animal model
  • Cognition
  • Hippocampus
  • Nicotine
  • Nicotinic receptor
  • Prefrontal cortex
  • Schizophrenia
  • Striatum
  • Working memory

ASJC Scopus subject areas

  • Pharmacology

Cite this

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title = "Nicotine effects in adolescence and adulthood on cognition and α4β2-nicotinic receptors in the neonatal ventral hippocampal lesion rat model of schizophrenia",
abstract = "Rational: Nicotine use in schizophrenia has traditionally been explained as {"}self-medication{"} of cognitive and/or nicotinic acetylcholinergic receptor (nAChR) abnormalities. Objectives: We test this hypothesis in a neurodevelopmental rat model of schizophrenia that shows increased addiction behaviors including enhanced nicotine reinforcement and drug-seeking. Methods: Nicotine transdermal patch (5 mg/kg/day vs. placebo∈×∈10 days in adolescence or adulthood) effects on subsequent radial-arm maze learning (15 sessions) and frontal-cortical-striatal nAChR densities (α4β2; [3H]-epibatidine binding) were examined in neonatal ventral hippocampal lesion (NVHL) and SHAM-operated rats. Results: NVHL cognitive deficits were not differentially affected by nicotine history compared to SHAMs. Nicotine history produced minimal cognitive effects while increasing food-reward consumption on the maze, compounding with NVHL-induced overconsumption. Acute nicotine (0.5 mg/kg) delivered before the final maze sessions produced modest improvements in maze performance in rats with nicotine patch histories only, but not differentially so in NVHLs. Consistent with in vivo neuroimaging of β2 nAChR binding in schizophrenia smokers vs. non-smokers and healthy controls, adult NVHLs showed 12{\%} reductions in nAChR binding in MPFC (p∈∈.40), whereas nicotine history elevated nAChRs across both regions (>30{\%}, p∈",
keywords = "Addiction, Animal model, Cognition, Hippocampus, Nicotine, Nicotinic receptor, Prefrontal cortex, Schizophrenia, Striatum, Working memory",
author = "Berg, {Sarah A.} and Sentir, {Alena M.} and Richard Bell and Eric Engleman and R. Chambers",
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T1 - Nicotine effects in adolescence and adulthood on cognition and α4β2-nicotinic receptors in the neonatal ventral hippocampal lesion rat model of schizophrenia

AU - Berg, Sarah A.

AU - Sentir, Alena M.

AU - Bell, Richard

AU - Engleman, Eric

AU - Chambers, R.

PY - 2015/5/1

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N2 - Rational: Nicotine use in schizophrenia has traditionally been explained as "self-medication" of cognitive and/or nicotinic acetylcholinergic receptor (nAChR) abnormalities. Objectives: We test this hypothesis in a neurodevelopmental rat model of schizophrenia that shows increased addiction behaviors including enhanced nicotine reinforcement and drug-seeking. Methods: Nicotine transdermal patch (5 mg/kg/day vs. placebo∈×∈10 days in adolescence or adulthood) effects on subsequent radial-arm maze learning (15 sessions) and frontal-cortical-striatal nAChR densities (α4β2; [3H]-epibatidine binding) were examined in neonatal ventral hippocampal lesion (NVHL) and SHAM-operated rats. Results: NVHL cognitive deficits were not differentially affected by nicotine history compared to SHAMs. Nicotine history produced minimal cognitive effects while increasing food-reward consumption on the maze, compounding with NVHL-induced overconsumption. Acute nicotine (0.5 mg/kg) delivered before the final maze sessions produced modest improvements in maze performance in rats with nicotine patch histories only, but not differentially so in NVHLs. Consistent with in vivo neuroimaging of β2 nAChR binding in schizophrenia smokers vs. non-smokers and healthy controls, adult NVHLs showed 12% reductions in nAChR binding in MPFC (p∈∈.40), whereas nicotine history elevated nAChRs across both regions (>30%, p∈

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