Perinatal exposure to the selective serotonin reuptake inhibitor citalopram alters spatial learning and memory, anxiety, depression, and startle in Sprague-Dawley rats

Autor: Arnold Gutierrez, Jillian R. Hufgard, Jenna L.N. Sprowles, Rebecca A. Bailey, Michael T. Williams, Charles V. Vorhees, Sarah A. Jablonski
Rok vydání: 2016
Předmět:
0301 basic medicine
Male
medicine.medical_specialty
Serotonin reuptake inhibitor
Spatial Learning
Morris water navigation task
Water maze
Citalopram
Anxiety
behavioral disciplines and activities
Reuptake
Marble burying
Rats
Sprague-Dawley
03 medical and health sciences
0302 clinical medicine
Sex Factors
Developmental Neuroscience
Pregnancy
Internal medicine
mental disorders
medicine
Animals
Maze Learning
Prepulse inhibition
Swimming
Depression
Amphetamines
Body Weight
Age Factors
Sensory Gating
Rats
030104 developmental biology
Endocrinology
Neuroprotective Agents
Animals
Newborn
Anesthesia
Prenatal Exposure Delayed Effects
Exploratory Behavior
Antidepressant
Female
Dizocilpine Maleate
Psychology
030217 neurology & neurosurgery
Selective Serotonin Reuptake Inhibitors
Developmental Biology
medicine.drug
Zdroj: International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience. 54
ISSN: 1873-474X
Popis: Selective serotonin reuptake inhibitors (SSRIs) block the serotonin (5-HT) reuptake transporter (SERT) and increase synaptic 5-HT. 5-HT is also important in brain development; hence when SSRIs are taken during pregnancy there exists the potential for these drugs to affect CNS ontogeny. Prenatal SSRI exposure has been associated with an increased prevalence of autism spectrum disorder (ASD), and peripheral 5-HT is elevated in some ASD patients. Perinatal SSRI exposure in rodents has been associated with increased depression and anxiety-like behavior, decreased sociability, and impaired learning in the offspring, behaviors often seen in ASD. The present study investigated whether perinatal exposure to citalopram causes persistent neurobehavioral effects. Gravid Sprague-Dawley rats were assigned to two groups and subcutaneously injected twice per day with citalopram (10mg/kg; Cit) or saline (Sal) 6h apart on embryonic day (E)6-21, and then drug was given directly to the pups after delivery from postnatal day (P)1-20. Starting on P60, one male/female from each litter was tested in the Cincinnati water maze (CWM) and open-field before and after MK-801. A second pair from each litter was tested in the Morris water maze (MWM) and open-field before and after (+)-amphetamine. A third pair was tested as follows: elevated zero-maze, open-field, marble burying, prepulse inhibition of acoustic startle, social preference, and forced swim. Cit-exposed rats were impaired in the MWM during acquisition and probe, but not during reversal, shift, or cued trials. Cit-exposed rats also showed increased marble burying, decreased time in the center of the open-field, decreased latency to immobility in forced swim, and increased acoustic startle across prepulse intensities with no effects on CWM. The results are consistent with citalopram inducing several ASD-like effects. The findings add to concerns about use of SSRIs during pregnancy. Further research on different classes of antidepressants, dose-effect relationships, timing of exposure periods, and mechanisms for these effects are needed. It is also important to balance the effects described here against the effects of the disorders for which the drugs are given.
Databáze: OpenAIRE
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