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Acute gonadotropin-releasing hormone agonist treatment enhances extinction memory in male rats.
Psychoneuroendocrinology. 2017 Aug; 82:164-172.P

Abstract

Leuprolide acetate (LEU), also known as Lupron, is commonly used to treat prostate cancer in men. As a gonadotropin-releasing hormone (GnRH) receptor agonist, it initially stimulates the release of gonadal hormones, testosterone (T) and estradiol. This surge eventually suppresses these hormones, preventing the further growth and spread of cancer cells. Individuals receiving this treatment often report anxiety and cognitive changes, but LEU's effects on the neural mechanisms that are involved in anxiety during the trajectory of treatment are not well known. In this study, we examined the acute effects of LEU on fear extinction, hypothesizing that increased T levels following a single administration of LEU will facilitate extinction recall by altering neuronal activity within the fear extinction circuitry. Two groups of naïve adult male rats underwent a 3-day fear conditioning, extinction, and recall experiment. The delayed group (n=15) received a single injection of vehicle or LEU (1.2mg/kg) 3weeks before behavioral testing. The acute group (n=25) received an injection one day after fear conditioning, 30min prior to extinction training. Following recall, the brains for all animals were collected for c-fos immunohistochemistry. Blood samples were also collected and assayed for T levels. Acute administration of LEU increased serum T levels during extinction training and enhanced extinction recall 24h later. This enhanced extinction memory was correlated with increased c-fos activity within the infralimbic cortex and amygdala, which was not observed in the delayed group. These results suggest that the elevation in T induced by acute administration of LEU can influence extinction memory consolidation, perhaps through modification of neuronal activity within the infralimbic cortex and amygdala. This may be an important consideration in clinical applications of LEU and its effects on anxiety and cognition.

Authors+Show Affiliations

Department of Psychiatry, Massachusetts General Hospital, Charlestown, MA, 02129, United States; Department of Psychiatry, Harvard Medical School, Boston, MA, 02115, United States. Electronic address: lmaeng@mgh.harvard.edu.Department of Psychiatry, Massachusetts General Hospital, Charlestown, MA, 02129, United States; Department of Psychiatry, Harvard Medical School, Boston, MA, 02115, United States.Department of Pharmacology, University of Maryland School of Medicine, Baltimore, MD, 20201, United States.Department of Psychiatry, Massachusetts General Hospital, Charlestown, MA, 02129, United States.Department of Psychiatry, Massachusetts General Hospital, Charlestown, MA, 02129, United States.Department of Psychiatry, Massachusetts General Hospital, Charlestown, MA, 02129, United States; Department of Psychiatry, Harvard Medical School, Boston, MA, 02115, United States.Department of Psychiatry, Massachusetts General Hospital, Charlestown, MA, 02129, United States; Department of Psychiatry, Harvard Medical School, Boston, MA, 02115, United States.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28550793

Citation

Maeng, L Y., et al. "Acute Gonadotropin-releasing Hormone Agonist Treatment Enhances Extinction Memory in Male Rats." Psychoneuroendocrinology, vol. 82, 2017, pp. 164-172.
Maeng LY, Taha MB, Cover KK, et al. Acute gonadotropin-releasing hormone agonist treatment enhances extinction memory in male rats. Psychoneuroendocrinology. 2017;82:164-172.
Maeng, L. Y., Taha, M. B., Cover, K. K., Glynn, S. S., Murillo, M., Lebron-Milad, K., & Milad, M. R. (2017). Acute gonadotropin-releasing hormone agonist treatment enhances extinction memory in male rats. Psychoneuroendocrinology, 82, 164-172. https://doi.org/10.1016/j.psyneuen.2017.05.015
Maeng LY, et al. Acute Gonadotropin-releasing Hormone Agonist Treatment Enhances Extinction Memory in Male Rats. Psychoneuroendocrinology. 2017;82:164-172. PubMed PMID: 28550793.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Acute gonadotropin-releasing hormone agonist treatment enhances extinction memory in male rats. AU - Maeng,L Y, AU - Taha,M B, AU - Cover,K K, AU - Glynn,S S, AU - Murillo,M, AU - Lebron-Milad,K, AU - Milad,M R, Y1 - 2017/05/17/ PY - 2017/01/08/received PY - 2017/04/13/revised PY - 2017/05/15/accepted PY - 2017/5/28/pubmed PY - 2018/4/4/medline PY - 2017/5/28/entrez KW - Anxiety KW - Fear extinction KW - Leuprolide acetate KW - Lupron KW - Testosterone KW - c-fos SP - 164 EP - 172 JF - Psychoneuroendocrinology JO - Psychoneuroendocrinology VL - 82 N2 - Leuprolide acetate (LEU), also known as Lupron, is commonly used to treat prostate cancer in men. As a gonadotropin-releasing hormone (GnRH) receptor agonist, it initially stimulates the release of gonadal hormones, testosterone (T) and estradiol. This surge eventually suppresses these hormones, preventing the further growth and spread of cancer cells. Individuals receiving this treatment often report anxiety and cognitive changes, but LEU's effects on the neural mechanisms that are involved in anxiety during the trajectory of treatment are not well known. In this study, we examined the acute effects of LEU on fear extinction, hypothesizing that increased T levels following a single administration of LEU will facilitate extinction recall by altering neuronal activity within the fear extinction circuitry. Two groups of naïve adult male rats underwent a 3-day fear conditioning, extinction, and recall experiment. The delayed group (n=15) received a single injection of vehicle or LEU (1.2mg/kg) 3weeks before behavioral testing. The acute group (n=25) received an injection one day after fear conditioning, 30min prior to extinction training. Following recall, the brains for all animals were collected for c-fos immunohistochemistry. Blood samples were also collected and assayed for T levels. Acute administration of LEU increased serum T levels during extinction training and enhanced extinction recall 24h later. This enhanced extinction memory was correlated with increased c-fos activity within the infralimbic cortex and amygdala, which was not observed in the delayed group. These results suggest that the elevation in T induced by acute administration of LEU can influence extinction memory consolidation, perhaps through modification of neuronal activity within the infralimbic cortex and amygdala. This may be an important consideration in clinical applications of LEU and its effects on anxiety and cognition. SN - 1873-3360 UR - https://www.unboundmedicine.com/medline/citation/28550793/Acute_gonadotropin_releasing_hormone_agonist_treatment_enhances_extinction_memory_in_male_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0306-4530(17)30010-0 DB - PRIME DP - Unbound Medicine ER -