Finné E

Effect of Nω‐nitro‐l‐arginine methyl ester, a nitric oxide synthesis inhibitor, on stress‐ and morphine‐induced prolactin release in male rats

The effect of the nitric oxide synthesis inhibitor Nω‐nitro‐l‐arginine methyl ester (l‐NAME) was investigated on stress‐ and morphine‐induced prolactin (PRL) secretion in vivo in male rats, by use of a stress‐free blood sampling and drug administration method by means of a permanent indwelling catheter in the right jugular vein. Three doses of l‐NAME were tested (1, 10 and 30 mg kg−1) and were given intraperitoneally one hour before blood sampling; control rats received saline. After the first blood sample, rats received an initial intravenous injection of morphine (3, 6 or 12 mg kg−1) or were subjected to immobilization stress. In the case of a morphine administration, rats received a second dose of morphine (3, 6 or 6 mg kg−1, respectively) 90 min later, when tolerance had developed, while rats subjected to immobilization stress received 6 mg kg−1 morphine 90 min after onset of stress. l‐NAME had no effect on basal plasma PRL concentration. However, it potentiated acute morphine‐induced PRL secretion and attenuated the subsequent tolerance in a dose‐dependent way. Immobilization stress‐induced PRL secretion was inhibited dose‐dependently by l‐NAME, as was its subsequent tolerance to morphine; however, in this case, in a reversed dose‐dependent way. When the highest dose of morphine (12 mg kg−1) was combined with the highest dose of l‐NAME pretreatment (30 mg kg−1), all rats showed a dramatic potentiation of the morphine‐induced PRL rise compared to controls. Moreover, all of these rats died within 90 min after the administration of morphine. These results show that NO plays a role in the acute opioid action on PRL release during stress as well as in the development of tolerance to the opioid effect, and some possible mechanisms are discussed.

Linear Percoll gradient centrifugation of rat anterior pituitary cells. A simple method for prolactin cell enrichment

Prolactin (PRL) cells were purified from nulliparous normal female adult Wistar rat pituitary cell suspensions by linear Percoll density gradient centrifugation, a procedure yielding single cells. Lactotrophs were found in two different layers, the first containing 70% PRL cells in the density range 1.055 to 1.065 g/ml, the second with 28% PRL cells in the range 1.070 to 1.080 g/ml. Both cell fractions contained more than 90% viable cells with an intact ultrastructure. The physiological integrity of the 70% enriched PRL cells was assessed by their basal PRL secretion, their secretory response to TRH and dopamine, and their cAMP production in a basal situation and after incubation with dopamine.

The effect of bombesin on basal, α-methyl-p-tyrosine, haloperidol, morphine, bremazocine and stress-induced prolactin secretion

Intravenously administered bombesin lowered basal PRL levels in conscious male rats and prevented the morphine, bremazocine and stress-induced PRL secretion. The same dose of bombesin had no effect on PRL levels in alpha-methyl-p-tyrosine pretreated rats and did not affect haloperidol-stimulated PRL release. These results show that bombesin given intravenously acts as an inhibitor of PRL secretion and suggests that it does not act on the lactotrope itself but rather by an increase of the inhibitory dopaminergic tone.

Opioid modulation of thyrotropin releasing hormone induced prolactin secretion

It is known that opioids stimulate prolactin (PRL) secretion by an action on hypothalamic neurons, but in vitro studies have suggested a direct action on the lactotrophs. The present study was performed on male rats known to have little or no PRL response to TRH. A beta-endorphin (beta EP) injection in the third ventricle stimulated PRL secretion and induced furthermore a PRL secretory reaction to TRH injected intravenously 20 min later. Pretreatment with naloxone 10 min before beta EP injection abolished not only the PRL response to beta EP but also the conjugated effect of beta EP and TRH. Pretreatment with naloxone methyl bromide (Br-naloxone), a quaternary naloxone derivative, which does not cross the blood-brain barrier, had no effect on the PRL response to beta EP but prevented the conjugated effect of beta EP and TRH on PRL secretion. Pretreatment of the animals with -methyl-parathyrosine resulting in a dopamine depletion or with haloperidol, a dopamine antagonist, could not induce lactotroph responsiveness to TRH. These results suggest that beta EP in male rat sensitizes the PRL cell to TRH by a direct effect and not through an inhibition of the dopaminergic tone.

In vivo and in vitro effect of naloxone on prolactin response to TRH in rat.

In adult male Wistar rats submitted to a standardized noise stress, intravenous TRH induced a prolactin (PRL) secretory response. Prior IV naloxone administration not only lowered plasma PRL levels in those stressed rats but abolished also the stimulatory action of TRH. This effect was further studied by superfusion experiments on enriched PRL cell suspensions (70% lactotrophs) from female adult Wistar rats. Naloxone kept unaffected the basal PRL secretion but lowered significantly that induced by TRH. These experiments suggest a dual effect of naloxone on rat PRL secretion, one exerted on central opioid receptors lowering stress-related increased basal PRL levels, the other inhibiting the TRH-dependent PRL secretion exerted at the lactotroph level itself.