Plasticity of presynaptic and postsynaptic serotonin 1A receptors in an animal model of epilepsy-associated depression

Eduardo A. Pineda, Julie G. Hensler, Raman Sankar, Don Shin, Teresa F. Burke, Andréy M. Mazarati

Research output: Contribution to journalArticlepeer-review

32 Scopus citations

Abstract

Depression is a common comorbidity of temporal lobe epilepsy and has highly negative impact on patients quality of life. We previously established that pilocarpine-induced status epilepticus (SE) in rats, concurrently with chronic epilepsy leads to depressive impairments, and that the latter may stem from the dysregulation of hypothalamo-pituitary-adrenocortical (HPA) axis and/or diminished raphe-hippocampal serotonergic transmission. We examined possible involvement of presynaptic and postsynaptic serotonin 1A (5-HT1A) receptors in epilepsy-associated depression. Based on their performance in the forced swim test (FST), post-SE animals were classified as those with moderate and severe depressive impairments. In moderately impaired rats, the activity of the HPA axis (examined using plasma corticosterone radioimmunoassay) was higher than in naive subjects, but the functional capacity of presynaptic 5-HT1A receptors (measured in raphe using autoradiography) remained unaltered. In severely depressed animals, both the activity of the HPA axis and the function of presynaptic 5-HT1A receptors were increased as compared with naive and moderately depressed rats. Pharmacological uncoupling of the HPA axis from raphe nucleus exerted antidepressant effects in severely impaired rats, but did not modify behavior in both naive and moderately depressed animals. Further, the function of postsynaptic 5-HT1A receptors was diminished in the hippocampus of post-SE rats. Pharmacological activation of postsynaptic 5-HT1A receptors improved depressive deficits in epileptic animals. We suggest that under the conditions of chronic epilepsy, excessively hyperactive HPA axis activates presynaptic 5-HT1A receptors, thus shifting the regulation of serotonin release in favor of autoinhibition. Downregulation of postsynaptic 5-HT1A receptors may further exacerbate the severity of epilepsy-associated depression.

Original languageEnglish (US)
Pages (from-to)1305-1316
Number of pages12
JournalNeuropsychopharmacology
Volume36
Issue number6
DOIs
StatePublished - May 2011

Keywords

  • comorbidity
  • depression
  • dorsal raphe
  • epilepsy
  • hypothalamo-pituitary-adrenocortical axis
  • serotonin 1A receptors

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health

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