PARADOXICAL EFFECTS OF DRUGS ACTING ON THE CENTRAL NERVOUS SYSTEM ON THE PREOVULATORY RELEASE OF PITUITARY LUTEINIZING HORMONE IN PRO-OESTROUS RATS

Abstract

There are many drugs which act on the central nervous system to block the spontaneous, preovulatory surge of LH in the plasma of the rat when administered just before the start of the LH surge at pro-oestrus. Several of these drugs have been tested for their ability to inhibit LH release after the start of the LH surge. Four day cyclic rats were each fitted with an indwelling right atrial cannula during the morning of pro-oestrus. Serial blood samples were collected through the cannula during the afternoon of pro-oestrus, starting at a time when the level of LH in the plasma was expected to be raised. Drugs were then administered at doses known to block the surge of LH. Additional blood samples were collected and subsequently the plasma concentration of LH was measured by radioimmunoassay. In rats with a raised level of LH, i.p. injection of phenobarbitone or pentobarbitone, s.c. injection of atropine or i.v. injection of ethanol caused the concentration of LH to fall rapidly starting within 15 min after the injection. The mean half-lives for the disappearance of LH from plasma ranged from 23·5 to 28·6 min over a 30 min period. In contrast, s.c. injection of nicotine, i.p. injection of urethane or continuous exposure to ether fumes resulted in a biphasic effect on the concentration of LH in the plasma. The value rose rapidly, reached a peak within 5–20 min and declined rapidly (range of mean half-lives 25·3– 28·6 min). Nicotine, urethane and ether caused a small, transient increase in the plasma level of LH when administered before the start of the spontaneous surge of LH. These results and the fact that luteinizing hormone releasing hormone (LH-RH) is far more effective at raising the concentration of LH in the plasma when given after the start of the LH surge than just before it, suggest that LH-RH must prime the pituitary gland before nicotine, urethane or ether can cause a substantial increase in the plasma level of LH in pro-oestrous rats.