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The behavioral effects of drugs stimulating prolactin (PRL) secretion have been studied in male rats. Acquisition of active avoidance behavior was facilitated by short- (SHPRL) and long-term hyperprolactinaemia (LHPRL) induced by pituitary homografts under the kidney capsule. Dopamine antagonists, such as haloperidol and bromperidol, though causing hyperprolactinaemia, suppressed the acquisition of active avoidance behavior. Sulpiride was not effective in this respect. SHPRL facilitated and LHPRL inhibited sexual behavior of male rats. Haloperidol, but not sulpiride, suppressed sexual capacity of these animals. Sulpiride and domperidone, but not haloperidol, increased locomotor activity of male rats. These data suggest that differences in the behavioral effects of dopamine antagonists may depend on their capacity to compete with PRL at the central level.

The present paper shows that a mixture of gangliosides (GA = GM1 + GD1a + GD1b + GT1b) is provided with a specific and powerful antinociceptive activity. The GA is active in reducing acetic acid and phenylquinone writhings, the acetic acid capillary-induced permeability and some acute inflammatory reactions. These actions seem to be mostly due to an anti-exudative property of the compounds which shows up right after the administration. The mixture of four gangliosides given in the proportion naturally occurring in the nervous system is more active than each single component in increasing the pain threshold, presenting therefore a synergistic effect. It is suggested that gangliosides can reduce the exudative phenomena interfering with the membrane permeability of the nerve-endings breaking interfering with the membrane permeability of the nerve-endings breaking the vicious circle of the neurogenic mechanisms of plasma extravasation.

Nerve growth factor (NGF) displays an inhibitory effect on peritoneal dye leakage in mice and on some types of acute inflammation in rats, i.e. acetic acid peritonitis and paw oedema induced by carrageenin, serotonin and dextran. Activity was only present in a restricted dose range, either after subcutaneous (1-8 micrograms/kg) or subplantar (0.5-5 micrograms) injection, and was characterized by a rapid onset of response. In the carrageenin test, NGF administered s.c. was more potent than indomethacin (INDO) and betamethasone (BTM); in addition, while the activity of INDO and BTM was observed only 2-3 hr after carrageenin challenge, the response of NGF developed within 1 hr, suggesting that NGF inhibits the early phase of the oedema. NGF exhibited a different action than BTM and INDO also in serotonin and dextran paw oedema. NGF (0.008 mg/kg s.c.) inhibited the serotonin oedema as early as 15 min and reached its maximum at 1 hr, whereas BTM (0.8 mg/kg) required at least 3 hr to attain the same effect. Serotonin oedema was not inhibited by INDO (even at 16 mg/kg) up to 0.25-6 hr, proving that this model of inflammation is insensitive to the inhibitors of prostaglandin synthesis. When given subplantary, NGF reduced dextran oedema, whereas BTM and INDO were ineffective. Pretreatment with specific anti-NGF antibodies abolished all the above effects of NGF, but did not modify the anti-inflammatory activity of BTM and INDO. NGF was less effective in reducing the exudate volume on carrageenin pleurisy and did not prevent cell migration. Tested in vitro, NGF showed no direct scavenging effect on superoxide radicals. These findings suggest that NGF may be involved in some types of acute inflammation by reducing vascular permeability.

The results of a broad pharmacological screening on a natural mixture of gangliosides (GA) and an inner ester (AGF1) are reported. Up to relatively high doses, GA and AGF1 did not affect general behavior and neurologic functions and were devoided of diuretic, antipyretic, ulcerogenic, antireserpine, antiapomorphine, anticholinergic and anticonvulsivant actions. Both compounds interfere specifically with some induced conditions of inflammation and pain, but AGF1 shows a stronger action in reducing phenylquinone writhing than GA which appears to possess a more pronounced anti-inflammatory activity. In the rat paw oedema the anti-inflammatory effect of GA and AGF1 developed 1 hr after carrageenin and reached its maximum at 2 hr, suggesting that an inhibition of the serotonin and kinin phases might be partly responsible. Therefore, it would seem that the anti-inflammatory action of gangliosides is not exerted by an inhibition of the prostaglandin (PG) system. This assumption is supported by the finding that GA and AGF1 did not influence yeast-induced hyperthermia nor produced ulcerogenic effects in fasted rats. Subcutaneous administration of AGF1 is less potent than indomethacin (2 times) in reducing phenylquinone writhings, but more effective than GA (6 times), codeine (9 times) and acetylsalicylic acid (187 times). After i.c.v. administration the anti-writhing activity of AGF1 was far more potent than that of all the other compounds. The neuronal substrate involved in the AGF1 antinociception is unknown at this time. The comparative study with GA suggests a dissociation between the anti-inflammatory activity and the antinociceptive response. The lack of analgesia in the hot plate test and the naloxone insensitive anti-writhing effect of AGF1 in mice indicate that a central opioid mechanism is not involved in the antinociceptive action. Furthermore, the negativity of the neurogenic plasma extravasation test seems to exclude also an interaction with peripheral opiate receptors. It is suggested that the antinociceptive action of AGF1 has both a peripheral and a central component via an interference with peripheral exsudative phenomena and the central serotonergic tonus.

Glutamic acid decarboxylase activity was assayed in rat substantia nigra, corpus striatum, medial basal hypothalamus and cerebellum under conditions of hyperprolactinemia induced by transplantation of adenopituitary under the kidney capsule. The results indicate that hyperprolactinemia induces a slight increase in the glutamic acid decarboxylase activity of substantia nigra and medial basal hypothalamus and a more evident increase at striatal level. No change was observed in the cerebellum.

Clonidine, injected i.p. 20 min before cold exposure, is able to counteract the blockade induced by alpha-methyl-p-tyrosine of cold-stimulated release of TSH in rats. Under basal conditions the alpha-adrenoceptor stimulating agent, administered into the lateral cerebral ventricle (10 microgram), produces, at 30 min, a sharp increase in plasma TSH that returns to control levels at 60 min. When the drug is given intraperitoneally (0.4 mg/kg) it causes a significant decrease in plasma TSH 120 min after the treatment.