Fear extinction in an obsessive-compulsive disorder animal model - influence of sex and estrous cycle

  • Type:#article
  • Year read:
  • Subject: OCD animal models fear extinction
  • Bibtex: @reimer2017
  • Bibliography: Reimer, A. E. et al. Fear extinction in an obsessive-compulsive disorder animal model: Influence of sex and estrous cycle. Neuropharmacology (2017). doi:10.1016/j.neuropharm.2017.12.015

Why and when I was reading this

Key takeaways

  • Adding a serotonin agonist increased grooming behavior in rats
  • Fear extinction was impaired in females

They treat rats with a serotonin agonist (mCPP). It increased grooming in both male and female rats. Fear extinction was impaired in females, and more so in females in the metestrus/diestrus phases of the estrous cycle.


Reproductive cycle events can influence symptom severity of OCD in females, indicating that ovarian hormones or their interaction with distinct neurotransmitter systems may play a role in OCD pathophysiology.

Clinical studies and animal models have confirmed the importance of the serotonergic (5-HT) system in the neurobiology and treatment of OCD. Accordingly, the non-selective 5-HT2c agonist, meta-chlorophenylpiperazine (mCPP), exacerbates symptoms in untreated OCD patients. In rodents, it evokes repetitive behaviors that engage brain areas that are homologous with those found to be dysfunctional in OCD patients.

Main results

Our results indicate that mCPP can induce OCD -like symptoms, exacerbating self- grooming and impairing fear extinction. It suggests that changes in 5-HT signaling through 5- HT2c receptors may have an important role in the OCD pathophysiology and that the influence of gonadal hormones in OCD should be further investigated.

Validity criteria of animal models

Predictive validity

Performance in the test predicts performance in the condition/situation being modelled

Face validity

Phenomenological similarity (etiology, biochemistry, symptomatology and treatment)

Construct validity

Theoretical rationale, demonstration of construct validity requires two things:

  1. Corresponding constructs are being studied in animals and humans. This presupposes that both the model and the disorder have been sufficiently studied to make an unambigious interpretation of the cognitive changes involved.
  2. A change in the construct is central to the disorder. This means that we must first understand mental disorders in people.