INHIBITION OF THE PREOVULATORY LH SURGE IN THE RAT BY CENTRAL NORADRENERGIC MEDIATION - INVOLVEMENT OF AN ANESTHETIC (URETHANE) AND OPIOID RECEPTOR AGONISTS

Endogenous opioid peptides play an important role in the generation of the pre-ovulatory LH surge, acting at specific receptor subtypes. It is thought that their effects in the regulation of GnRH and LH may be exerted by interacting with the other brain neurotransmitter systems e .g. aminergic systems. We have further investigated the interrelations hip between the opioid and aminergic systems in the control of GnRH ac tivity and LH secretion, and involvement of mu- and kappa-opioid subty pes in this process. Urethane-anaesthetised or conscious female rats w ere intraperitoneally injected with mu- (diamorphine) or kappa-agonist (U-50,488H) before the critical period on pro-oestrus. Amine content of medial preoptic area (MPOA), suprachiasmatic nucleus (SCN), median eminence (ME) and arcuate nucleus (ARN) was simultaneously determined by HPLC-ECD. Plasma LH levels were measured by RIA. In the controls, t he LH surge was pronounced and noradrenaline (NA) levels (pg/mu g prot ein, M+/-SEM) were high (MPOA 34.5+/-1.5; SCN 35.1+/-2.5; ME 33.2+/-1. 7; ARN 33.1+/-1.9). Both mu- and kappa-agonists significantly decrease d the NA concentrations in all areas examined (p<0.01) concomitant wit h inhibition of the LH surge. Dopamine levels were selectively reduced only by the mu-agonist in the MPOA (p<0.01). In the urethane-anaesthe tised rats, the expected LH surge was totally inhibited and NA concent rations were reduced in all animals. The present study provides furthe r evidence to support the hypothesis that an increase in hypothalamic NA activity is a critical event in triggering the surge release of GnR H and LH. Both the mu- and kappa-opioid subtypes may be involved in th e inhibition of the pre-ovulatory LH surge. It is also concluded that care should be taken when using general anaesthetics in neuroendocrine studies.