Proof for histaminergic but not for adrenergic involvement in the growth hormone-releasing effect of an enkephalin analog in the dog.

A series of studies was performed in unanesthetized dogs to ascertain whether, in addition to cholinergic pathways, other neurotransmitter systems were involved in the GH-releasing effect of the potent enkephalin analog [D-Ala2, MePhe4, Met(o)5-ol]enkephalin (DAMME). DAMME at a dose of 8 microgram/kg iv elicited a striking rise in plasma canine GH (cGH), with peak levels at 30 min. Blockade of histaminergic H1 receptors by diphenhydramine (30 mg,iv, 15 min before) or clemastine (1 mg orally three times for 2 days and 2 mg orally 60 min before) completely suppressed the cGH release induced by DAMME without significantly altering baseline cGH levels. A slight reduction of the effect of DAMME was also induced by the histamine H2 receptor antagonist cimetidine (300 mg, iv, 15 min before). Pretreatment with the alpha-adrenergic inhibitor phentolamine (0.4 mg/min for 45 min) did not alter the neuroendocrine effect of DAMME, despite the occurrence of a rise in blood glucose (peak levels, 185 +/- 47 mg/dl). The administration of propranolol, a blocker of beta-receptors, did not potentiate the cGH release induced by a threshold dose of DAMME (4 microgram/kg, iv). An iv bolus injection of glucose (1 g/kg), which induced peak glucose levels of 296 +/- 29 mg/dl, completely suppressed the cGH release induced by DAMME or propranolol plus DAMME. These results indicate that histaminergic H1 receptors play an important role in the cGH release induced by DAMME, whereas this action occurs independently from adrenergic mediation. Based on these and previous findings, a neuromodulator role in GH-releasing mechanisms is suggested for opioid peptides.

Neuroleptic-induced prolactin rise: influence of pharmacological alterations of different neurotransmitter system.

Oral administration of 2 neuroleptic drugs, haloperidol and LR511 induced in male rats a marked, dose-dependent and sustained rise of plasma prolactin.

Classical neuroleptics and deconditioning activity after single or repeated treatment. Role of different cerebral neurotransmitters.

A dose-dependent inhibition of conditioned avoidance response (CAR) was documented in trained rats after acute treatment with several neuroleptics: haloperidol, chlorpromazine (CPZ), fluanisone and 4-p-fluorophenyl-5-N(N'-o-methoxyphenyl)piperazinoethyl-4-oxazolin-2-one (zoloperone, LR 511). The compounds differently affected the unconditioned escape response (UER), haloperidol and LR 511 being almost inactive. Daily treatment with LR 511 or haloperidol for 7-16 days did not cause the appearance of tolerance in young and adult rats, on the contrary, made in evidence a stronger effect on CAR and on UER. This supersensitive state towards the neuroleptics did not disappear even after 30 days' treatment interruption. The acute administration of some neuroleptics in combination with other centrally active drugs, endowed with different mechanism of action, yielded the following results on CAR: amphetamine (a dopaminergic stimulant) readily antagonized the effect of LR 511 and haloperidol; chlorpheniramine and diphenhydramine (antihistaminics) minimized the effect of small doses of LR 511 and haloperidol while they did not alter that of larger doses; atropine (an anti-cholinergic), metergoline (an anti-5-hydroxytryptaminic (5-HT) and cyproheptadine (an anti-5-HT possessing antihistaminic and anticholinergic properties) protentiated the effect of LR 511 while in part reduced that of haloperidol. CPZ, which was associated only with atropine, behaved like LR 511. The role of various brain neurotransmitters is discussed.