Faculty Collaboration Database

Involvement of the endocannabinoid system in the ability of long-term tricyclic antidepressant treatment to suppress stress-induced activation of the hypothalamic-pituitary-adrenal axis. Neuropsychopharmacology 2006 Dec;31(12):2591-9

Date

05/20/2006

Pubmed ID

16710317

DOI

10.1038/sj.npp.1301092

Scopus ID

2-s2.0-33748712399 (requires institutional sign-in at Scopus site)   108 Citations

Abstract

The efficacy of antidepressants has been linked in part to their ability to reduce activity of the hypothalamic-pituitary-adrenal (HPA) axis; however, the mechanism by which antidepressants regulate the HPA axis is largely unknown. Given that recent research has demonstrated that endocannabinoids can regulate the HPA axis and exhibit antidepressant potential, we examined the hypothesis that the endocannabinoid system is regulated by long-term antidepressant treatment. Three-week administration of the tricyclic antidepressant desipramine (10 mg/kg/day) resulted in a significant increase in the density of the cannabinoid CB(1) receptor in the hippocampus and hypothalamus, without significantly altering endocannabinoid content in any brain structure examined. Furthermore, chronic desipramine treatment resulted in a reduction in both secretion of corticosterone and the induction of the immediate early gene c-fos in the medial dorsal parvocellular region of the paraventricular nucleus of the hypothalamus (PVN) following a 5 min exposure to swim stress. Acute treatment with the CB(1) receptor antagonist, AM251 (1 mg/kg), before exposure to swim stress, completely occluded the ability of desipramine to reduce both corticosterone secretion and induction of c-fos expression in the PVN. Collectively, these data demonstrate that CB(1) receptor density in the hippocampus and hypothalamus is increased by chronic tricyclic antidepressant treatment, and suggest that this upregulation could contribute to the ability of tricyclic antidepressants to suppress stress-induced activation of the HPA axis.

Author List

Hill MN, Ho WS, Sinopoli KJ, Viau V, Hillard CJ, Gorzalka BB

Author

Cecilia J. Hillard PhD Associate Dean, Center Director, Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Antidepressive Agents, Tricyclic
Cannabinoid Receptor Modulators
Cortisone
Depressive Disorder, Major
Desipramine
Disease Models, Animal
Drug Administration Schedule
Endocannabinoids
Gene Expression Regulation
Hippocampus
Hypothalamo-Hypophyseal System
Male
Norepinephrine
Paraventricular Hypothalamic Nucleus
Piperidines
Proto-Oncogene Proteins c-fos
Pyrazoles
Rats
Rats, Sprague-Dawley
Receptor, Cannabinoid, CB1
Stress, Psychological
Up-Regulation