Francesco Spadaro

Effects of vinburnine on experimental models of learning and memory impairments

Retrograde amnesia can be induced experimentally in mice by injecting them with scopolamine (3 mg/kg, IP) or by inducing seizures with pentylenetetrazol (50 mg/kg, IP), and in rats by subjecting them to hypobaric hypoxia (at a barometric pressure of 300 mmHg for 3 min). We have studied the effects of vinburnine (VNB) in these amnesic states compared to vincamine (VNC) and nicergoline (NCG), in order to assess its activity on drug-induced learning and memory impairments. Vinburnine reduced the disrupting effect of both scopolamine and pentylenetetrazol-induced seizures on the retention of a step-through passive avoidance behavior in mice and on the acquisition of shuttle-box active avoidance behavior in rats. This effect was dose-related up to 20 mg/kg, the peak effect dose after IP administration, and more pronounced than that of VNC and NCG in some tests. These results indicate that VNB influences learning and memory processes disrupted by a pharmacological manipulation. In particular, as scopolamine acts as anticholinergic drug, it is possible that VNB mechanism of action includes also a stimulation of acetylcholine neurotransmission.

Memory deficits of aged male rats can be improved by pyrimidine nucleosides and n-acetyl-glutamine

The pyrimidine nucleosides uridine (URI) and cytidine (CYT), alone or associated with n-acetyl-glutamine (NAG), were injected acutely or subchronically to aged (26 months old) male rats of the Sprague-Dawley strain. Learning and memory abilities of the animals were studied with tests of avoidance behavior. The acquisition of active avoidance behavior was studied with the shuttle-box test. A step-through type of passive avoidance task was used to examine the retention of passive avoidance responses. The acquisition of the active avoidance behavior and the retention of the passive avoidance response were reduced in aged animals as compared with those of young animals. Neither the acute treatment of old rats with URI and CYT alone nor that associated with NAG exerted any effect on the behavioral tests. In contrast, the subchronic treatment with URI and CYT was followed by a facilitation of acquisition of active avoidance behavior in the shuttle box and of retention of passive avoidance responses in the dark box. A more potent effect on the acquisition of the shuttle-box behavior and on the retention of passive avoidance reaction was found in animals treated subchronically with the pyrimidine nucleosides associated with NAG. These effects may be related to the role of pyrimidines in the synthesis of ribonucleic acid, which is indispensable for learning and memory processes.

Acetylcarnitine reduces the immobility of rats in a despair test (constrained swim).

Male rats forced to swim in a cylinder adopted an immobile posture. Immobility was reduced by acetylcarnitine (5, 10, and 20 mg/kg) and by antidepressant drugs, such as desipramine and iproniazid, injected 24, 5, and, again, 1 h prior to behavioral testing. Acetylcarnitine also potentiated the anti-immobility effect of antidepressant drugs in the despair test. Chronic (10 days) treatment with acetylcarnitine mimicked the effect found after acute administration. It is possible that the action of the acetylcarnitine on the despair test is indicative of an antidepressant activity of this drug that is dependent on a change in the sensitivity of monoamine receptors in the brain.

Prolactin as a Protective Factor in Stress‐Induced Gastric Ulcers

57. STREMPLE, J. F. 1976. Am. J. Surg. 131: 78-85. 58. HERNANDEZ, D. E. & G. A. MASON. In Ulcer Disease: New Aspects of Pathogenesis and Pharmacology, Vol. 1. S. Szabo & C. J. Pfeiffer, Eds.: 207-215. CRC Press. Boca Raton, FL. 59. SZABO, S., A. W. SANDROCK, J. NAFRADI, E. A. MAULL, G. T. GALLAGHER & A. BLYZNIUK. 1982. I n Advances in the Biosciences, Vol. 37. M. Kohsaka, T. Shohmori, Y. Tsukada, & G. N. Woodruff, Eds.: 165-170, Pergamon Press. New York, NY. Ed.: 301-333. Raven Press. New York, NY.

Protective action of phosphatidylserine on stress-induced behavioral and autonomic changes in aged rats.

Phosphatidylserine (PS) was administered in aged rats subjected to various stressor stimuli in order to evaluate its effect on grooming behavior, core temperature and gastric ulcers. Novelty-induced grooming appeared to be increased in aged rats as compared to young controls. The subchronic intraperitoneal treatment with PS (20 mg/kg/day for 20 days) decreased grooming activity in aged rats, whereas it did not affect that of young animals. Restraint stress induced hyperthermia in both aged and young rats. However, 90 min after the beginning of restraint, PS-treated old rats showed a normalization of core temperature. Furthermore, restraint-plus-cold stress induced gastric ulcers in both aged and young rats. The treatment with PS was followed by a decreased incidence of gastric lesions in aged, but not in young rats. The mechanism of PS protective action against stress-induced behavioral and autonomic changes is unknown, but it may involve the brain level as this drug exerts a noteworthy influence on behavior and autonomic functions.

Role of Prolactin in Stress-Induced Biological Modifications in Animals

It is well established that the adenohypophyseal hormone prolactin (PRL) is released in high quantity by animals subjected to stress of physical and psychological nature. Swingle et al. (1951) first described the occurrence of pseudopregnancy in female rats subjected to different types of stressor stimuli. Later, it was found that stress promotes milk secretion, suggesting the possible involvement of PRL (Nicoll et al., 1960). In 1965, Grosvenor et al. described in detail the stress-induced depletion of PRL from the adenohypophysis. However, it is not yet clear whether this hyperprolactinemia is just the consequence of a general hypothalamic activation induced by stress or it plays any role in the biological phenomena caused by the application of stress.

Behavioral Changes Induced by Neonatal Administration of TRH Antiserum

The possible involvement of TRH in brain maturation, as suggested by various findings,I4 has been studied by using a specific TRH antiserum in three-day-old rats and evaluating the consequent behavioral changes at different times after treatment. Pregnant female rats of the Wistar strain were used. After the delivery, the pups were maintained in the mothers cage until they were one month old. Afterwards, they were caged separately. TRH antiserum was raised in rabbits against synthetic rat TRH using keyhole-limpet hemocyanin as a carrier protein and glutaraldehyde as a coupling agent. TRH antiserum was injected i.p. in a single administration at day 3 after birth, and normal rabbit serum was injected in control animals. No significant difference was observed between animals treated with TRH antiserum and controls in the development of the neonatal reflexes, righting, forelimb grasping, and forelimb placing reflexes (TABLE 1). A significant reduction