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Updated: Aug 25, 2026
Restraint to Induce Stress in Mice and Rats
Published on: December 6, 2024
Rearing condition and rh5-HTTLPR interact to influence limbic-hypothalamic-pituitary-adrenal axis response to stress
Christina S Barr1, Timothy K Newman, Courtney Shannon
1Laboratory of Clinical Studies, National Institute of Alcoholism and Alcohol Abuse, National Institutes of Health, Poolesville, Maryland 20837, USA.
Background:
In humans and macaques, a promoter polymorphism that decreases transcription of the serotonin transporter gene is associated with anxiety. Serotonin transporter gene disruption in rodents produces anxious animals with exaggerated limbic-hypothalamic-pituitary-adrenal (LHPA) responses to stress. We wanted to determine whether serotonin transporter gene promoter variation (rh-5HTTLPR) and rearing condition would interact to influence endocrine responses to stress in infant rhesus macaques.
Methods:
Animals were reared with their mothers (MR, n = 141) or in peer-only groups (PR, n = 67). At 6 months of age, adrenocorticotropic hormone (ACTH) and cortisol levels were determined at baseline and during separation stress. Serotonin transporter genotype (l/l and l/s) was determined with polymerase chain reaction followed by gel electrophoresis.
Results:
Cortisol levels increased during separation, and there was a main effect of rearing condition, with decreased cortisol levels among PR macaques. Animals with l/s rh5-HTTLPR genotypes had higher ACTH levels than did l/l animals. Adrenocorticotropic hormone levels increased during separation, and there was a separation x rearing x rh5-HTTLPR interaction, such that PR-l/s animals had higher ACTH levels during separation than did other animals studied.
Conclusions:
These data demonstrate that serotonin transporter gene variation affects LHPA axis activity and that the influence of rh5-HTTLPR on hormonal responses during stress is modulated by early experience.
