Neonatal testosterone modifies LH secretion in the adult female rat by altering the opioid-noradrenergic interaction in the medial preoptic area.

Noradrenergic-opioid interaction in the medial preoptic area (MPOA) was examined in ovariectomised adult rats which were oestrogen-treated and had been injected neonatally with either testosterone propionate (TP) or vehicle (oil). The first experiment involved electrical stimulation of the ventral noradrenergic tract (VNAT) in anaesthetised rats. Blood samples were collected before and after the stimulation to determine plasma levels of luteinising hormone (LH). Approximately half of the animals received naloxone i.v. 15 min before the onset of stimulation. In all groups, stimulation of VNAT elicited a significant increase in plasma LH concentration. However, pretreatment with naloxone in androgenised rats, but not in oil-treated animals, almost doubled the LH increment due to stimulation. Naloxone had no effect on plasma LH concentrations in unstimulated control rats. In the second experiment hypothalamic slices containing the MPOA were preincubated with [3H]noradrenaline [( 3H]NA) and then subjected to electrical field stimulation under the conditions of (a) no drug added and (b, c) morphine superfusion without and with naloxone. The opioid agonist morphine significantly reduced the net release of [3H]NA in normal and TP-treated female rats. Addition of equimolar naloxone reversed this effect in normal females, whereas in the androgenised group it not only reversed this effect but elicited a significant increase in [3H]NA release. From these data we conclude that (1) neonatal testosterone treatment alters noradrenergic-opioid interaction regulating LH secretion in adult females and (2) the site of this change may be the presynaptic opioid input to the noradrenergic terminals in the MPOA.