Increased responsiveness of presumed 5-HT cells to citalopram in adult rats subjected to prolonged maternal separation relative to brief separation

Lotta Arborelius, Brian W. Hawks, Michael J. Owens, Paul M. Plotsky, Charles Nemeroff

Research output: Contribution to journalArticle

78 Citations (Scopus)

Abstract

Rationale: Certain adverse events in childhood, such as loss of a parent or sexual abuse, are associated with an increased vulnerability to develop depression later in life. Prolonged, daily maternal separation of rat pups induces several behavioral, endocrine and neurochemical changes similar to those observed in human depression. Objectives: Because dysfunction of brain serotonergic systems has been implicated in the pathophysiology of depression, the effects of neonatal maternal separation on these systems was studied in adult rats. Methods: Male rat pups were subjected to daily maternal separation for 180 min (HMS180) from postnatal day 2 to day 14. Neonatal handled rats, i.e., pups undergoing daily 15-min separations during the same time period (HMS15), were chosen as a control group, since the 180-min separations involved handling of the pups, i.e., the pups were removed from the home cage during the separations. As adults, the effect of citalopram (0.05-0.80 mg/kg, intravenous) on the firing rate of 5-HT neurons in the dorsal raphe nucleus (DRN) was studied. Results: The inhibitory effect of citalopram on serotonergic cell firing was significantly enhanced at doses of 0.1 mg/kg and 0.4 mg/kg in the HMS180 compared with that in the HMS15 rats. However, the number of binding sites and mRNA expression of the 5-HT transporter and 5-HT1A receptors in the DRN did not differ between the two rearing groups. Conclusion: These findings suggest that early life stress gives rise to persistent changes in the function, but not the density or mRNA expression of central 5-HT 1A receptors and/or 5-HT transporters.

Original languageEnglish
Pages (from-to)248-256
Number of pages9
JournalPsychopharmacology
Volume176
Issue number3-4
DOIs
StatePublished - Nov 1 2004
Externally publishedYes

Fingerprint

Citalopram
Serotonin
Mothers
Receptor, Serotonin, 5-HT1A
Depression
Messenger RNA
Sex Offenses
Psychological Stress
Binding Sites
Neurons
Control Groups
Brain

Keywords

  • 5-HT transporter
  • 5-HT receptor
  • Citalopram
  • In situ hybridization
  • In vivo electrophysiology
  • Maternal separation
  • Receptor binding autoradiography

ASJC Scopus subject areas

  • Pharmacology

Cite this

Increased responsiveness of presumed 5-HT cells to citalopram in adult rats subjected to prolonged maternal separation relative to brief separation. / Arborelius, Lotta; Hawks, Brian W.; Owens, Michael J.; Plotsky, Paul M.; Nemeroff, Charles.

In: Psychopharmacology, Vol. 176, No. 3-4, 01.11.2004, p. 248-256.

Research output: Contribution to journalArticle

Arborelius, Lotta ; Hawks, Brian W. ; Owens, Michael J. ; Plotsky, Paul M. ; Nemeroff, Charles. / Increased responsiveness of presumed 5-HT cells to citalopram in adult rats subjected to prolonged maternal separation relative to brief separation. In: Psychopharmacology. 2004 ; Vol. 176, No. 3-4. pp. 248-256.
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