Opiate antagonist treatment reinstates estrous cycles in middle-aged persistent-estrous rats

Middle-aged female rats display luteinizing hormone (LH) surge deficits and cycle irregularity followed by the onset of persistent estrus (PE). The central nervous system has been identified as a primary locus of failure in PE rats, but the particular neural elements involved have not been determined. The goal of the present study was to identify a role for endogenous opioid peptides (EOP) in age-related acyclicity by evaluating the effect of opiate antagonist treatment on vaginal cytology in PE rats. PE rats were administered, s.c., saline (SAL), naloxone (NAL) or naltrexone (NTX) once daily for 20 days, or repetitively on Day 1 and on successive proestrus days if cyclicity was resumed. Single NTX (50 mg/kg), but not NAL (2 mg/kg), treatment interrupted the PE state in almost half of treated animals. Daily or repetitive proestrus NTX (10 mg/kg) treatment interrupted PE more frequently, and many animals displayed repeated estrous cycles and ovulation. Afternoon LH surges were observed after initial NTX treatment in animals displaying PE interruption. This demonstration that LH surges and ovulatory cycles can be reinitiated in PE rats with NTX suggests that dysfunction in the 'brake' on EOP secretion during proestrus may be one of the neuroendocrine impairments mediating acyclicity in aging female rats.