Prenatal Exposure to Nicotine Impairs Performance of the 5-Choice Serial Reaction Time Task in Adult Rats

Institute of Psychiatry, King's College London, London, UK.
Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology (Impact Factor: 7.05). 02/2011; 36(5):1114-25. DOI: 10.1038/npp.2010.249
Source: PubMed


Cigarette smoking is associated with a wide variety of adverse reproductive outcomes, including increased infant mortality and decreased birth weight. Prenatal exposure to tobacco smoke, of which nicotine is a major teratogenic component, has also been linked to the acceleration of the risk for different psychiatric disorders, including conduct disorder and attention deficit hyperactivity disorder (ADHD). Whether this increased risk is influenced by the direct effects of gestational nicotine exposure on the developing fetus remains uncertain. In this study we provide experimental evidence for the effects of prenatal nicotine exposure on measures of attention and impulsivity in adult male rats. Offspring of females exposed during pregnancy to 0.06 mg/ml nicotine solution as the only source of water (daily consumption: 69.6±1.4 ml/kg; nicotine blood level: 96.0±31.9 ng/ml) had lower birth weight and delayed sensorimotor development measured by negative geotaxis, righting reflex, and grip strength. In the 5-choice serial reaction time test, adult rats showed increased numbers of anticipatory responses and omissions errors, more variable response times, and lower accuracy with evidence of delayed learning of the task demands when the 1 s stimulus duration was introduced. In contrast, prenatal nicotine exposure had no effect on exploratory locomotion or delay-discounting test. Prenatal nicotine exposure increased expression of the D5 dopamine receptor gene in the striatum, but did not change expression of other dopamine-related genes (DRD4, DAT1, NR4A2, and TH) in either the striatum or the prefrontal cortex. These data suggest a direct effect of prenatal nicotine exposure on important aspects of attention, inhibitory control, or learning later in life.

Download full-text


Available from: Lisiane Bizarro, Oct 02, 2015
22 Reads
  • Source
    • "This exposure has also been shown to have a genetic component in that pups of prenatally exposed pups also show behavioral impairments (Zhu et al, 2014). Previous studies have shown that prenatal nicotine exposure via drinking water at the same dose used in our study (0.06 mg/ml) produces increased anticipatory responses on the five-choice serial reaction time task in rats (Schneider et al, 2011). Similar results have been obtained in mice, where prenatal nicotine exposure via drinking water reduces cingulate cortex volume, reduces prefrontal dopamine turnover, and induces hyperactivity, which was diminished by oral methylphenidate treatment (Zhu et al, 2012). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Prenatal nicotine exposure (PNE) is linked to numerous psychiatric disorders including attention deficit hyperactivity disorder (ADHD). Current literature suggests that core deficits observed in ADHD reflect abnormal inhibitory control governed by the prefrontal cortex. Yet, it is unclear how neural activity in the medial prefrontal cortex (mPFC) is modulated during tasks that assess response inhibition or if these neural correlates, along with behavior, are affected by PNE. To address this issue, we recorded from single mPFC neurons in control and PNE rats as they performed a stop-signal task. We found that PNE rats were faster for all trial-types, made more premature responses, and were less likely to inhibit behavior on 'STOP' trials during which rats had to inhibit an already initiated response. Activity in mPFC was modulated by response direction and was positively correlated with accuracy and movement time in control but not PNE rats. Although the number of single neurons correlated with response direction was significantly reduced by PNE, neural activity observed on general STOP trials was largely unaffected. However, dramatic behavioral deficits on STOP trials immediately following non-conflicting (GO) trials in the PNE group appear to be mediated by the loss of conflict monitoring signals in mPFC. We conclude that prenatal nicotine exposure makes rats impulsive and disrupts firing of mPFC neurons that carry signals related to response direction and conflict monitoring.Neuropsychopharmacology accepted article preview online, 20 July 2015. doi:10.1038/npp.2015.197.
    Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology 07/2015; DOI:10.1038/npp.2015.197 · 7.05 Impact Factor
    • "One week prior to training, animals began habituation to daily handling and weighing, and to the chambers and food reward (45-mg sucrose pellets, Bio-Serv, Flemington, NJ). Food restriction was applied (ϳ6 g of food/100 g of body weight) in order to maintain body weight at 85% to 90% of their freefeeding weight (Bari, Dalley, & Robbins, 2008; Schneider et al., 2011). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Attention-deficit hyperactivity disorder (ADHD) may be caused by genetic or environmental factors. Among environmental factors, perinatal complications are related, such as neonatal hypoxia-ischemia (HI). Thus, the aim of this study was to investigate whether HI contributes to the development of characteristics related to ADHD in adult rats, and to correlate the behavioral results with brain damage volume. Male Wistar rats were divided into 2 groups: HI and control. The HI procedure consisted of a permanent occlusion of the right common carotid artery followed by a period of hypoxia (90 min; 8% O₂ and 92% N₂) on the 7th postnatal day. Two months later, animals were evaluated in the open field test during a single 5-min session, and in the 5-choice serial reaction time task (5-CSRTT), over 25 weeks. Our results demonstrated that animals submitted to HI manifest cognitive impairments in task acquisition, deficits in sustained attention, and increases in impulsivity and compulsivity in response to task manipulation in the 5-CSRTT. Locomotor activity observed in open field did not differ between groups. Moreover, brain volume loss in the total hemisphere, cerebral cortex, white matter, hippocampus, and striatum were observed in HI animals, especially on the side ipsilateral to the lesion. From these results, we can infer that neonatal HI is an environmental factor that could contribute to the development of behavioral characteristics observed in ADHD that are associated with general brain atrophy. (PsycINFO Database Record (c) 2015 APA, all rights reserved).
    Behavioral Neuroscience 06/2015; 129(3):309-320. DOI:10.1037/bne0000063 · 2.73 Impact Factor
  • Source
    • "Visual attention training tasks included (listed in order of difficulty): 60 s-stimulus duration (light on); 30 s-stimulus duration; 10 s-stimulus duration; and 5 s-stimulus duration. All animals were moved on to the next training task together when all group averages reached 70% correct responses [62]. For all training tasks, the inter-trial interval was held constant at 5 s, but the position of the light for each trial varied. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Hypoxia-ischemia (HI) occurs when blood and/or oxygen delivery to the brain is compromised. HI injuries can occur in infants born prematurely (<37 weeks gestational age) or at very low birth weight (<1500 grams), as well as in term infants with birth complications. In both preterm and term HI populations, brain injury is associated with subsequent behavioral deficits. Neonatal HI injury can be modeled in rodents (e.g., the Rice-Vannucci method, via cautery of right carotid followed by hypoxia). When this injury is induced early in life (between postnatal day (P)1-5), neuropathologies typical of human preterm HI are modeled. When injury is induced later (P7-12), neuropathologies typical of those seen in HI term infants are modeled. The current study sought to characterize the similarities/differences between outcomes following early (P3) and late (P7) HI injury in rats. Male rats with HI injury on P3 or P7, as well as sham controls, were tested on a variety of behavioral tasks in both juvenile and adult periods. Results showed that P7 HI rats displayed deficits on motor learning, rapid auditory processing (RAP), and other learning/memory tasks, as well as a reduction in volume in various neuroanatomical structures. P3 HI animals showed only transient deficits on RAP tasks in the juvenile period (but not in adulthood), yet robust deficits on a visual attention task in adulthood. P3 HI animals did not show any significant reductions in brain volume that we could detect. These data suggest that: 1) behavioral deficits following neonatal HI are task-specific depending on timing of injury; 2) P3 HI rats showed transient deficits on RAP tasks; 3) the more pervasive behavioral deficits seen following P7 HI injury were associated with substantial global tissue loss; and 4) persistent deficits in attention in P3 HI subjects might be linked to neural connectivity disturbances rather than a global loss of brain volume, given that no such pathology was found. These combined findings can be applied to our understanding of differing long-term outcomes following neonatal HI injury in premature versus term infants.
    Behavioural brain research 10/2013; 259. DOI:10.1016/j.bbr.2013.10.038 · 3.03 Impact Factor
Show more