Inhibition of the pre-ovulatory LH surge in the rat by central noradrenergic mediation: Involvement of an anaesthetic (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 interrelationship between the opioid and aminergic systems in the control of GnRH activity and LH secretion, and involvement of mu- and kappa-opioid subtypes in this process. Urethane-anaesthetised or conscious female rats were 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, the LH surge was pronounced and noradrenaline (NA) levels (pg/mu g protein, 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 decreased the NA concentrations in all areas examined (p<0.01) concomitant with inhibition of the LH surge. Dopamine levels were selectively reduced only by the mu-agonist in the MPOA (p<0.01). In the urethane-anaesthetised rats, the expected LH surge was totally inhibited and NA concentrations were reduced in all animals. The present study provides further evidence to support the hypothesis that an increase in hypothalamic NA activity is a critical event in triggering the surge release of GnRH and LH. Both the mu- and kappa-opioid subtypes may be involved in the inhibition of the pre-ovulatory LH surge. It is also concluded that care should be taken when using general anaesthetics in neuroendocrine studies.