Relationships between arousal and cognition-enhancing effects of oxiracetam.

Cognition-enhancing effects of no-otropic drugs are currently ascribed to an increase in arousal level. In order to test this hypothesis, we studied the effects of three doses of oxiracetam (25, 50 and 100 mg/kg IP) on a radial maze task and on slow wave sleep (SWS) latency in a familiar environment. The 25- and 100-mg/kg doses, but not the 50-mg/kg, significantly improved performance in the memory task. On the other hand, SWS latency was significantly increased by 50 and 100 mg/kg, with the effect of the 25-mg/kg dose going in the same direction but only approaching significance. These results give only a partial support to the "arousal factor hypothesis." Other factors are probably involved in the promnesic effects of oxiracetam.

Spatial but not object recognition is impaired by aging in rats.

Four groups of male Wistar rats (4, 8, 18, and 24 months) were submitted to object recognition and spatial recognition tests. Object recognition was not significantly affected by aging even at a longer retention interval. On the contrary, spatial recognition was significantly impaired in 18- and 24-month groups. The existence of two dissociable neural systems, respectively involved in object and spatial recognition, is discussed.

Gene expression of tyrosine hydroxylase in the developing fetal brain.

Tyrosine hydroxylase, aromatic L-amino-acid decarboxylase, and dopamine beta-hydroxylase activities were studied in the developing fetal rat brain. A delay of 2-3 days between the detection of the tyrosine hydroxylase and the aromatic L-amino-acid decarboxylase and dopamine beta-hydroxylase activities was observed. For this reason, the expression of tyrosine hydroxylase mRNA was studied. Tyrosine hydroxylase mRNA was visualized in the whole brain from 13 days of gestation, but the largest increase of the expression was observed in the hypothalamus. These results are discussed in terms of the relative gene expressions of the three enzymes involved in the biosynthesis of catecholamines and phenolamines in nervous tissues.

Effects of aging on p- and m-octopamine, catecholamines, and their metabolizing enzymes in the rat.

Functions of octopamine in the mammalian brain are still not well known. An important aspect of this problem is the relationship between octopamines and catecholamines. Previous data have shown that their respective ontogenic evolutions are not parallel. Do the changes in brain related to aging also differentially affect these two groups of molecules? In order to check this point, the brain levels of p- and m-octopamine, p-tyramine, noradrenaline, and dopamine, as well as the activities of metabolizing enzymes, were determined in young adult and aging rats (20-26 months). Unlike catecholamines, there is a drastic decrease of p-octopamine after 20 months of age in the hypothalamus and telencephalon. p-Tyramine levels are also lowered. This change appears to be due to a decrease of the aromatic L-amino acid decarboxylase activity. These data, as those of ontogenic studies, confirm that p-octopamine and catecholamine metabolisms may have some independent steps and, moreover, that p-octopamine may have a role in the normal activity of the brain.

A new one-trial test for neurobiological studies of memory in rats. II: Effects of piracetam and pramiracetam.

The effects of the nootropic drugs Piracetam (Pir) and Pramiracetam (Pram) were evaluated on recognition-memory of rats in a new one-trial test. This test is based on spontaneous exploratory activity and does not involve rule learning or reinforcement. Recognition is measured by the time spent by rats in exploring two different objects, one familiar (the sample), the other new. When the retention interval is 1 min, normal rats spend more time exploring the new object which demonstrates that they recognize the familiar one, but they do not discriminate between the two objects after a 24-h interval. Three doses of Pram (15, 30 and 60 mg/kg) and Pir (100, 200 and 400 mg/kg) were administered i.p. 30 min before the acquisition trial. The doses of 30 mg/kg of Pram and of 400 mg/kg of Pir produced a significant improvement in retention when the intertrial interval was 24 h. This effect was not associated with a change in overall exploratory behavior. This study shows that the new object-recognition test may be a useful tool for pharmacological studies of memory in rats.

Prenatal ontogenesis of brain phenolamines and catecholamines in relation to their metabolizing enzymes in Roman avoider strains of rats.

Phenolamines, particularly octopamines, are of special importance in avoidance behavior. In the Roman low avoidance (RLA) strain, p-octopamine can induce locomotor behavioral activity that is normally observed in the Roman high avoidance (RHA) strain. For these reasons, the levels of prenatal octopamines (para and meta isomers) have been studied in relation to noradrenaline and dopamine levels. In the hypothalamus and brainstem of RHA, a maximum level of the para isomer is observed at 15 days of embryonic development but, unlike in controls and RLA animals, this level remains almost constant until 20 days. For the meta-isomer and catecholamines, there is a 1-2 day delay in detection between controls and RLA or RHA. The study of related enzyme activities reveals that tyrosine hydroxylase displays a 2-day delay in RHA when compared to the control value at 19 days of fetal life. These results are discussed in terms of the role of p-octopamine in avoidance conditioning and of the possible delayed expression of the tyrosine hydroxylase gene in Roman strains of rats.

Effects of piracetam on learned helplessness in rats.

In rats, the effects of Piracetam (P), the prototype of nootropic drugs, were studied on a very widely used model of behavioral disturbance: the learned helplessness (LH) phenomenon. In this model, exposure to uncontrollable and unsignalled shocks impairs subsequent escape-avoidance learning. In a first experiment, this deficit was abolished by 200 mg/kg of P, and to a lesser extent, by a 100 mg/kg dose, administered before the training session. In non-stressed animals, no dose of P was able to have a facilitatory effect on escape-avoidance. In a second experiment, the administration of P, not before the training session as in Experiment I, but before the stress, had no effect on the LH phenomenon regardless of the dose.

Prenatal ontogenesis of p-, m-octopamine and phenylethanolamine in relation to catecholamines and their metabolizing enzymes in the developing rat brain and heart.

Non-catecholamines such as phenylethanolamine and p-octopamine are present in many invertebrate nervous systems, sometimes in large amounts. These amines are normally present in the rat brain at much lower levels, p- and m-octopamine are present at trace levels in the mammalian brain. The prenatal development of these amines was studied in comparison with those of noradrenaline and dopamine. The activities of tyrosine hydroxylase, dopa decarboxylase, dopamine beta-hydroxylase and monoamine oxidase were determined in parallel. Phenylethanolamine and p-octopamine are more abundant in the brain between 13 and 17 fetal days than dopamine and noradrenaline but decrease after 17 days whereas the levels of m-octopamine and the two catecholamines increase afterwards. Dopa decarboxylase, dopamine beta-hydroxylase and tyrosine hydroxylase are detected early in fetal life (13, 15 and 14.5 days respectively) but monoamine oxidase activity was not found before 18 days.

[Ontogenetic analysis of the theta rhythm during paradoxical sleep in rats]. / Analyse ontogénétique du rythme thêta, au cours du sommeil paradoxal, chez le rat.

In the rat, an ontogenetic study of theta rhythm during paradoxical sleep shows a clear evolution between the 14th and the 30th postnatal day. During this period, its mean frequency increases from 5 to 7 cycles per second, and its spectrum shows significant changes. These parameters (mean frequency and spectral components) of the theta rhythm could be a useful index of brain maturation in the rat.