Antonia G. Nasello

Effect of learning and of drugs on the ribonucleic acid concentration of brain structures of the rat.

Abstract Hippocampal RNA concentration of rats was increased by: (a) One intraperitoneal injection of saline solution; (b) ten daily intraperitoneal injections of saline solution; (c) one intraperitoneal injection of amphetamine or nicotine; (d) one session of 25-min duration, of avoidance conditioning; (e) six daily sessions of 15 min each, of avoidance conditioning. The increases observed upon single amphetamine or nicotine injections were significant when values were compared to those of rats receiving one saline injection, taken as controls. The acute conditioning procedure led, in addition, to an increase in neocortical RNA. An acute pseudoconditioning procedure was without effect on hippocampal and neocortical RNA. The injection of saline solution was considered to involve a sequence of stimuli characteristic of a conditioning procedure, and the results obtained upon such injections were correspondingly interpreted. Animals which received ten daily injections of strychnine or amphetamine had a lower hippocampal RNA content than those which received ten daily saline injections. The chronic treatment with nicotine or strychnine raised cerebellar RNA levels. The results suggest: (a) A link between the learning process and the action of drugs known to favor learning, on one hand, and hippocampal RNA synthesis, on the other; (b) the possibility of a cerebellar site of action for nicotine and strychniine.

Effects of Cannabidiol and of Diphenylhydantoin on the Hippocampus and on Learning

Cannabidiol (3.5 mg/kg, i.p.) depressed hippocampal facilitation and posttetanic potentiation of evoked responses in rats, such, as had been reported before for diphenylhydantoin. Both diphenylhydantoin (80 mg/kg, i.p.) and cannabidiol blocked the increase of hippocampal RNA concentration caused by afferent stimulation, and depressed the acquisition of a conditioned avoidance response in rats. Neither drug affected the retention of such response when given by posttrial injection, nor the spontaneous locomotor activity of mice. The effects of both agents may be explained by the interference they have been previously shown to produce with the release of K+ from the hippocampus during stimulation. In fact, hippocampal facilitation and posttetanic potentiation and the RNA response to stimulation have been shown to be phenomena which depend on this K+ release, and have been attributed a role in learning.

Effects on the acquisition of conditioned avoidance responses and seizure threshold in the offspring of amphetamine treated gravid rats

Female rats with 30 to 70% of conditioned responses in an avoidance conditioning session in a Warner cage, were treated daily during pregnancy with 0.5 mg/kg of d,l-amphetamine administered subcutaneously. They had been mated with males selected with the same criterion who received no treatment.The control group differed from the treated one in that females received the same volume of saline solution instead of the drug.Teratogenic effects of the drug were not observed and there were no differences in either the age of eyes or vaginal aperture or in growth rate determined by the weekly weight between offspring of treated and control mothers.The pups of amphetamine treated mothers had better acquisition and retention of conditioned avoidance responses than those of control mothers when they were 90 days old but no difference was observed at the age of 45 days.On the other hand, offspring of the treated group had a lower hippocampal seizure threshold than the control group.The relation between the mechanisms of learning and seizure are discussed in connection with potassium release by stimulation in the hippocampus.

Pharmacological evidence that hippocampal facilitation, posttetanic potentiation and seizures may be due to a common mechanism

Abstract Pieces of filter paper soaked in veratrine, tetraethylamnonium, and diphenylhidantoin solutions were placed on the alveus. Facilitation of hippocampal evoked responses was enhanced by the former and depressed by the latter two drugs. The number of 10/sec stimuli to either the fornix or the contralateral alveus needed to cause a seizure was reduced by veratrine and increased by tetraethylammonium and diphenylhidantoin. Diphenylhidantoin, besides, had a depressant effect on hippocampal homosynaptic and heterosynaptic posttetanic potentiation. These data correlate with those previosuly reported by us on the effect of veratrine and tetraethylammonium on posttetanic potentiation and on spike complications and support the hypothesis that the occurrence of hippocampal facilitation, posttetanic potentiation and seizures are all dependent on a (K+)0 accumulation brought about by the firing of afferent fibers within the local restricted extracellular space.

Brain catecholamines metabolism in offspring of amphetamine treated rats.

Previous observations have pointed out that treatment with amphetamine during pregnancy produces behavioral modifications in adulthood. In order to elucidate some possible brain biochemical mechanisms that could explain the behavioral changes observed we have determined the endogenous content of brain dopamine and noradrenaline, the in vivo rate of conversion of tyrosine-C14 in such amines and the activity of tyrosine-hydroxylase, the rate limiting enzyme in catecholamines biosynthesis. We did not observe modifications in the endogenous content of dopamine and noradrenaline but did observe an increase in the conversion rate of tyrosine-C14 in such amines and also in the tyrosine-hydroxylase activity. These results indicate that treatment with amphetamines during fetal age produces catecholamine metabolism modifications that persist throughout adulthood, although the influence of behavioral modifications of the mothers cannot be ruled out. The relationship with behavioral changes is discussed.

Prenatal amphetamine exposure: Ovulation, sexual behavior and hypothalamic monoamine content in rats

Previous observations have pointed out that amphetamine treatment during pregnancy produces behavioral and neurochemical changes in the male offspring. The present study was undertaken in order to determine whether those findings could be extended to sexual behavior, reproductive function and hypothalamic monoamine metabolism in female rats. It was found that offspring of amphetamine treated rats have greater sensitivity to estrogen and estrogen-progesterone for the induction of sexual receptivity. 5-HT content in medial hypothalamus of estrogen-progesterone treated rats was decreased with respect to controls. On the other hand the content of 5-HIAA was not different; noradrenaline levels in hypothalamus were also normal. Sex cycle duration and ovulatory phenomena were not affected.

Effect of potassium on hippocampal ribonucleic acid concentration

Abstract A cannula with normal (3.2 mEq) or higher than normal (7, 11, 25 mEq) K + concentrations was placed on the hippocampus; this was considered artificially to cause corresponding modifications of (K + ) 0 . Up to 11 mEq, K + produced an increase of total hippocampal RNA concentration, and 25 mEq caused a decrease. The increase was attributed to an enhancement of spike-dependent transmitter release, as it was antagonized by 15 mEq Mg ++ and by 30 mEq procaine. The possibility was considered that the increase of RNA was dependent on pyramidal cell firing, which would be enhanced by increased synaptic efficiency. Procaine, in the presence of normal K + , lowered the hippocampal RNA concentration. The decrease of hippocampal RNA found with 25 mEq K + was related to the induction of seizures and to stimulation of the Na + -K + pump.

Effect of morphine on the RNA and ATP concentration of brain structures of the rat.

The effect of morphine on rat cortical, hippocampal, thalamic, and hypothalamic RNA and ATP concentration was studied. After a single dose (10 mg/kg, i.p.) there was an increase of RNA in the cortex and thalamus, and a decrease of ATP levels in both structures. When the drug was given chronically (daily injections during 10 days at increasing doses from 10 to 100 mg/kg), only a fall of thalamic RNA and an increase of thalamic ATP were observed relative to saline-treated controls. Rats which received the chronic saline treatment, however, had higher hippocampal thalamic RNA and levels and a lower thalamic ATP concentration than those which received a single saline Injection.

Effects of Some Cholinergic, Adrenergic and Serotoninergic Compounds, Glutamic Acid and GABA on Hippocampal Seizures

The dorsal hippocampus of rats was perfused with solutions of Ach, NA, 5-HT, GA, GABA, atropine, eserine, hexamethonium, dibenamine, nethalide, α-MT, methysergide and p-CPA, in order to determine their effect on the number of stimuli to the fornix needed, at 10-second rates, to cause a hippocampal seizure. Ach, 5-HT and GA reduced this number, and NA and GABA increased it. Eserine had an effect similar to that of Ach, whereas atropine had an opposite one, and, in addition, it antagonized that of Ach. Dibenamine and α-MT acted oppositely to NA, and the former, in addition, antagonized the effect of NA. Methysergide and p-CPA had an effect opposite to that of 5-HT, and methysergide antagonized that of the latter. With the method used by us it cannot be determined if the antagonisms atropine-Ach, dibenamine-NA and methysergide-5-HT are competitive, noncompetitive or merely a sum of effects. Neither hexamethonium nor nethalide had any effect of their own on the number of stimuli needed to cause a seizure.

Effect of veratrine and tetraethylammonium on hippocampal homosynaptic and heterosynaptic post-tetanic potentiation.

Abstract Homosynaptic and heterosynaptic post-tetanic potentiation of hyppocampal field responses to subicular and commisural stimulation were enhanced by the topical application of veratrine on the alveus, and depressed by that of tetraethylammonium. On the basis of known data on the action of these drugs on K+ conductance, the present findings are interpreted as a support to the hypothesis that hippocampal homosynaptic and heterosynaptic post-tetanic potentiation are due to a (K+)0 accumulation.