Ovariectomy ameliorates dextromethorphan--induced memory impairment in young female rats.
We have previously found that dextromethorphan (DM), over-the-counter cough suppressant, impairs memory retention in water maze task, when it is repeatedly administrated to adolescent female rats at high doses. In this study we examined first if ovariectomy ameliorates the DM-induced memory impairment in female rats, and then whether or not the DM effect is revived by estrogen replacement in ovariectomized female rats. Female rat pups received bilateral ovariectomy or sham operation on postnatal day (PND) 21, and then intraperitoneal DM (40 mg/kg) daily during PND 28-37. Rats were subjected to the Morris water maze task from PND 38, approximately 24 h after the last DM injection. In probe trial, goal quadrant dwell time was significantly reduced by DM in the sham operated group, however, the reduction by DM did not occur in the ovariectomy group. When 17beta-estradiol was supplied to ovariectomized females during DM treatment, the goal quadrant dwell time was significantly decreased, compared to the vehicle control group. Furthermore, a major effect of estrogen replacement was found in the escape latency during the last 3 days of initial learning trials. These results suggest that ovariectomy may ameliorate the adverse effect of DM treatment on memory retention in young female rats, and that estrogen replacement may revive it, i.e. estrogen may take a major role in DM-induced memory impairment in female rats.
Department of Pharmacology Yonsei University College of Medicine, Shin Chon Dong, Seo Dae Moon Ku, Seoul, 120-752, Korea. jwjahng@yumc.yonsei.ac.kr
Jeong Won
JW
Jahng
Hee Jeong
HJ
Cho
Jae Goo
JG
Kim
Nam Youl
NY
Kim
Seoul
S
Lee
Yil Seob
YS
Lee
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003915:Dextromethorphan / Q000633:toxicity*; D004195:Disease Models, Animal; D015914:Estrogen Replacement Therapy / Q000009:adverse effects*; D004967:Estrogens / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects*; D008569:Memory Disorders / Q000139:chemically induced / Q000628:therapy*; D008570:Memory, Short-Term; D010052:Ovariectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014867:Water / Q000502:physiology
D004967:Estrogens; D014867:Water; D003915:Dextromethorphan