Influence of developmental nicotine exposure on serotonergic control of breathing-related motor output

Lila Wollman, Andrew Hill, Brady Hasse, Christina Young, Giovanni Hernandez-De La Pena, Richard B. Levine, Ralph F. Fregosi

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1 Scopus citations


Serotonin plays an important role in the development of brainstem circuits that control breathing. Here, we test the hypothesis that developmental nicotine exposure (DNE) alters the breathing-related motor response to serotonin (5HT). Pregnant rats were exposed to nicotine or saline, and brainstem–spinal cord preparations from 1- to 5-day-old pups were studied in a split-bath configuration, allowing drugs to be applied selectively to the medulla or spinal cord. The activity of the fourth cervical ventral nerve roots (C4VR), which contain axons of phrenic motoneurons, was recorded. We applied 5HT alone or together with antagonists of 5HT1A, 5HT2A, or 5HT7 receptor subtypes. In control preparations, 5HT applied to the medulla consistently reduced C4VR frequency and this reduction could not be blocked by any of the three antagonists. In DNE preparations, medullary 5HT caused a large and sustained frequency increase (10 min), followed by a sustained decrease. Notably, the transient increase in frequency could be blocked by the independent addition of any of the antagonists. Experiments with subtype-specific agonists suggest that the 5HT7 subtype may contribute to the increased frequency response in the DNE preparations. Changes in C4VR burst amplitude in response to brainstem 5HT were uninfluenced by DNE. Addition of 5HT to the caudal chamber modestly increased phasic and greatly increased tonic C4VR activity, but there were no effects of DNE. The data show that DNE alters serotonergic signaling within brainstem circuits that control respiratory frequency but does not functionally alter serotonin signaling in the phrenic motoneuron pool.

Original languageEnglish (US)
Pages (from-to)175-191
Number of pages17
JournalDevelopmental Neurobiology
Issue number2
StatePublished - Mar 2022


  • brainstem
  • control of breathing
  • phrenic motoneuron
  • serotonin receptors
  • spinal cord

ASJC Scopus subject areas

  • Developmental Neuroscience
  • Cellular and Molecular Neuroscience


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