Blockade of serotonin 5-HT2A receptors potentiates dopamine D2 activation-induced disruption of pup retrieval on an elevated plus maze, but has no effect on D2 blockade-induced one

Lina Nie, Tianqi Di, Yu Li, Peng Cheng, Ming Li, Jun Gao

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Appetitive aspect of rat maternal behavior, such as pup retrieval, is motivationally driven and sensitive to dopamine disturbances. Activation or blockade of dopamine D2 receptors causes a similar disruption of pup retrieval, which may also reflect an increase in maternal anxiety and/or a disruption of executive function. Recent work indicates that serotonin 5-HT2A receptors also play an important role in rat maternal behavior. Given the well-known modulation of 5-HT2A on the mesolimbic and mesocortical dopamine functions, the present study examined the extent to which blockade of 5-HT2A receptors on dopamine D2-mediated maternal effects using a pup retrieval on the elevated plus maze (EPM) test. Sprague-Dawley postpartum female rats were acutely injected with quinpirole (a D2 agonist, 0.10 and 0.25 mg/kg, sc), or haloperidol (a D2 antagonist, 0.1 or 0.2 mg/kg, sc), in combination of MDL100907 (a 5-HT2A receptor antagonist, 1.0 mg/kg, sc, 30 min before quinpirole or haloperidol injection) or saline and tested at 30, 90 and 240 min after quinpirole or haloperidol injection on postpartum days 3 and 7. Quinpirole and haloperidol decreased the number of pup retrieved (an index of maternal motivation) and sequential retrieval score (an index of executive function), prolonged the pup retrieval latencies, reduced the percentage of time spent on the open arms (an index of maternal anxiety), and decreased the distance travelled on the maze in a dose-dependent and time-dependent fashion. MDL100907 treatment by itself had no effect on pup retrieval, but it exacerbated the quinpirole-induced disruption of pup retrieval, but had no effect on the haloperidol-induced one. These findings suggest a complex interactive effect between 5-HT2A and D2 receptors on one or several maternal processes (maternal motivation, anxiety and executive function), and support the idea that one molecular mechanism by which 5-HT2A receptors mediate maternal behavior is through its modulation of D2 receptors.

Original languageEnglish (US)
Pages (from-to)74-84
Number of pages11
JournalPharmacology Biochemistry and Behavior
Volume171
DOIs
StatePublished - Aug 1 2018

Fingerprint

Quinpirole
Receptor, Serotonin, 5-HT2A
Haloperidol
Dopamine
Maternal Behavior
Chemical activation
Mothers
Executive Function
Rats
Anxiety
Postpartum Period
Motivation
Modulation
Serotonin 5-HT2 Receptor Antagonists
Injections
Dopamine D2 Receptors

Keywords

  • Dopamine D
  • Haloperidol
  • Maternal behavior
  • MDL100907
  • Quinpirole
  • Serotonin 5-HT

ASJC Scopus subject areas

  • Biochemistry
  • Toxicology
  • Pharmacology
  • Clinical Biochemistry
  • Biological Psychiatry
  • Behavioral Neuroscience

Cite this

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title = "Blockade of serotonin 5-HT2A receptors potentiates dopamine D2 activation-induced disruption of pup retrieval on an elevated plus maze, but has no effect on D2 blockade-induced one",
abstract = "Appetitive aspect of rat maternal behavior, such as pup retrieval, is motivationally driven and sensitive to dopamine disturbances. Activation or blockade of dopamine D2 receptors causes a similar disruption of pup retrieval, which may also reflect an increase in maternal anxiety and/or a disruption of executive function. Recent work indicates that serotonin 5-HT2A receptors also play an important role in rat maternal behavior. Given the well-known modulation of 5-HT2A on the mesolimbic and mesocortical dopamine functions, the present study examined the extent to which blockade of 5-HT2A receptors on dopamine D2-mediated maternal effects using a pup retrieval on the elevated plus maze (EPM) test. Sprague-Dawley postpartum female rats were acutely injected with quinpirole (a D2 agonist, 0.10 and 0.25 mg/kg, sc), or haloperidol (a D2 antagonist, 0.1 or 0.2 mg/kg, sc), in combination of MDL100907 (a 5-HT2A receptor antagonist, 1.0 mg/kg, sc, 30 min before quinpirole or haloperidol injection) or saline and tested at 30, 90 and 240 min after quinpirole or haloperidol injection on postpartum days 3 and 7. Quinpirole and haloperidol decreased the number of pup retrieved (an index of maternal motivation) and sequential retrieval score (an index of executive function), prolonged the pup retrieval latencies, reduced the percentage of time spent on the open arms (an index of maternal anxiety), and decreased the distance travelled on the maze in a dose-dependent and time-dependent fashion. MDL100907 treatment by itself had no effect on pup retrieval, but it exacerbated the quinpirole-induced disruption of pup retrieval, but had no effect on the haloperidol-induced one. These findings suggest a complex interactive effect between 5-HT2A and D2 receptors on one or several maternal processes (maternal motivation, anxiety and executive function), and support the idea that one molecular mechanism by which 5-HT2A receptors mediate maternal behavior is through its modulation of D2 receptors.",
keywords = "Dopamine D, Haloperidol, Maternal behavior, MDL100907, Quinpirole, Serotonin 5-HT",
author = "Lina Nie and Tianqi Di and Yu Li and Peng Cheng and Ming Li and Jun Gao",
year = "2018",
month = "8",
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doi = "10.1016/j.pbb.2018.06.004",
language = "English (US)",
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T1 - Blockade of serotonin 5-HT2A receptors potentiates dopamine D2 activation-induced disruption of pup retrieval on an elevated plus maze, but has no effect on D2 blockade-induced one

AU - Nie, Lina

AU - Di, Tianqi

AU - Li, Yu

AU - Cheng, Peng

AU - Li, Ming

AU - Gao, Jun

PY - 2018/8/1

Y1 - 2018/8/1

N2 - Appetitive aspect of rat maternal behavior, such as pup retrieval, is motivationally driven and sensitive to dopamine disturbances. Activation or blockade of dopamine D2 receptors causes a similar disruption of pup retrieval, which may also reflect an increase in maternal anxiety and/or a disruption of executive function. Recent work indicates that serotonin 5-HT2A receptors also play an important role in rat maternal behavior. Given the well-known modulation of 5-HT2A on the mesolimbic and mesocortical dopamine functions, the present study examined the extent to which blockade of 5-HT2A receptors on dopamine D2-mediated maternal effects using a pup retrieval on the elevated plus maze (EPM) test. Sprague-Dawley postpartum female rats were acutely injected with quinpirole (a D2 agonist, 0.10 and 0.25 mg/kg, sc), or haloperidol (a D2 antagonist, 0.1 or 0.2 mg/kg, sc), in combination of MDL100907 (a 5-HT2A receptor antagonist, 1.0 mg/kg, sc, 30 min before quinpirole or haloperidol injection) or saline and tested at 30, 90 and 240 min after quinpirole or haloperidol injection on postpartum days 3 and 7. Quinpirole and haloperidol decreased the number of pup retrieved (an index of maternal motivation) and sequential retrieval score (an index of executive function), prolonged the pup retrieval latencies, reduced the percentage of time spent on the open arms (an index of maternal anxiety), and decreased the distance travelled on the maze in a dose-dependent and time-dependent fashion. MDL100907 treatment by itself had no effect on pup retrieval, but it exacerbated the quinpirole-induced disruption of pup retrieval, but had no effect on the haloperidol-induced one. These findings suggest a complex interactive effect between 5-HT2A and D2 receptors on one or several maternal processes (maternal motivation, anxiety and executive function), and support the idea that one molecular mechanism by which 5-HT2A receptors mediate maternal behavior is through its modulation of D2 receptors.

AB - Appetitive aspect of rat maternal behavior, such as pup retrieval, is motivationally driven and sensitive to dopamine disturbances. Activation or blockade of dopamine D2 receptors causes a similar disruption of pup retrieval, which may also reflect an increase in maternal anxiety and/or a disruption of executive function. Recent work indicates that serotonin 5-HT2A receptors also play an important role in rat maternal behavior. Given the well-known modulation of 5-HT2A on the mesolimbic and mesocortical dopamine functions, the present study examined the extent to which blockade of 5-HT2A receptors on dopamine D2-mediated maternal effects using a pup retrieval on the elevated plus maze (EPM) test. Sprague-Dawley postpartum female rats were acutely injected with quinpirole (a D2 agonist, 0.10 and 0.25 mg/kg, sc), or haloperidol (a D2 antagonist, 0.1 or 0.2 mg/kg, sc), in combination of MDL100907 (a 5-HT2A receptor antagonist, 1.0 mg/kg, sc, 30 min before quinpirole or haloperidol injection) or saline and tested at 30, 90 and 240 min after quinpirole or haloperidol injection on postpartum days 3 and 7. Quinpirole and haloperidol decreased the number of pup retrieved (an index of maternal motivation) and sequential retrieval score (an index of executive function), prolonged the pup retrieval latencies, reduced the percentage of time spent on the open arms (an index of maternal anxiety), and decreased the distance travelled on the maze in a dose-dependent and time-dependent fashion. MDL100907 treatment by itself had no effect on pup retrieval, but it exacerbated the quinpirole-induced disruption of pup retrieval, but had no effect on the haloperidol-induced one. These findings suggest a complex interactive effect between 5-HT2A and D2 receptors on one or several maternal processes (maternal motivation, anxiety and executive function), and support the idea that one molecular mechanism by which 5-HT2A receptors mediate maternal behavior is through its modulation of D2 receptors.

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KW - Quinpirole

KW - Serotonin 5-HT

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DO - 10.1016/j.pbb.2018.06.004

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JO - Pharmacology Biochemistry and Behavior

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