Nikolaos Pitsikas

Effects of the active constituents of Crocus sativus L., crocins on recognition and spatial rats' memory.

Crocus sativus L. is a plant cultivated in various parts of the world. Its involvement in learning and memory processes has been proposed. Crocins are water-soluble carotenoids and are among the active components of C. sativus L. The present study was designed to investigate in the rat the effects of crocins on recognition and spatial memory. For this aim, the object recognition task which evaluates non-spatial working memory and a novel version of the radial water maze which assesses spatial reference and spatial working memory were chosen. In a first study, crocins (15 and 30mg/kg) counteracted delay-dependent recognition memory deficits in the normal rat, suggesting that these carotenoids modulate storage and/or retrieval of information. In a subsequent study, treatment with crocins (30mg/kg and to a lesser extent also 15mg/kg) attenuated scopolamine (0.2mg/kg)-induced performance deficits in the radial water maze test. The present results support and extend the enhancing effects of crocins on memory and, then, to our knowledge, for the first time, demonstrate its implication in the mechanisms underlying recognition and spatial memory.

Effect of Life-Long Hypocaloric Diet on Age-Related Changes in Motor and Cognitive Behavior in a Rat Population

Aged (24 months), adult (12 months), and young (4 months) rats kept on standard or hypocaloric diets from the age of three weeks old were tested in a range of behavioral tests to determine the effects of aging on sensory-motor and cognitive behavior and to assess whether such effects were prevented by life-long calorie restriction. An age-related deterioration of sensory-motor functions, motility and exploratory activity was observed in all the senescent animals independent of diet. Swimming ability did not deteriorate with age. Spatial memory, evaluated by the Morris water maze test, showed some deterioration in normally fed adult rats as indicated by the deceleration in the learning curve. In aged rats, not only was learning slowed down, but memory utilization was also impaired. These cognitive deficiencies were absent in rats fed the hypocaloric diet.

Crocus sativus L. extracts antagonize memory impairments in different behavioural tasks in the rat

The effects of extracts of Crocus sativus L. (CSE), on memory were investigated in the rat by using the object recognition and the step-through passive avoidance task. In the first study, post-training administration of CSE (30 and 60 g/kg) successfully counteracted extinction of recognition memory in the normal rat, suggesting that CSE modulates storage and/or retrieval of information. In a subsequent study, pre-training treatment with CSE (30 and 60 mg/kg) significantly antagonized the scopolamine (0.75 mg/kg)-induced performance deficits in the step-through passive avoidance test. These results support and extend prior findings about the implication of CSE in learning and memory mechanisms.

The 5-HT1A receptor antagonist WAY 100635 improves rats performance in different models of amnesia evaluated by the object recognition task

The effects of the 5-HT(1A) receptor antagonist WAY 100635 on recognition memory were investigated in two different amnestic models in the rat by using the object recognition task. WAY 100635 at 1 mg/kg, but not at 0.3 mg/kg, counteracted scopolamine-induced performance deficits in the acquisition version of this behavioral paradigm. At the same dose, WAY 100635 antagonized extinction of recognition memory in the normal rat, suggesting that it affected acquisition, storage and retrieval of information. These results support and extend prior findings that interactions between the serotonergic and cholinergic systems are relevant to cognition and indicate that WAY 100635 modulates different aspects of recognition memory.

Aging and food restriction: Effect on lipids of cerebral cortex

In experimental animals dietary restriction reduces the body weight increase due to aging, increases longevity and delays the onset of age-related physiological deterioration, including age-related changes in serum lipids. Little is known about the influence of food restriction on brain lipids, whose concentration and composition have been shown to change with age. We studied whether some biochemical and biophysical parameters of rat brain membranes, known to be modified with age, were affected by a diet low in calories, in which 50% of lipids and 35% of carbohydrates have been replaced by fibers. The diet was started at weaning and maintained throughout the animals entire life span. Animals fed the low calorie diet survived longer and gained less body weight than standard diet fed rats. Age-related increases in microviscosity, cholesterol/phospholipid and sphingomyelin/phosphatidylcholine ratios were reduced or restored to the levels of young animals in cortex membranes of 32 old rats fed the low calorie diet, while the age-related increase in mono- to polyunsaturated fatty acid ratios in phospholipids was further raised. In conclusion we have shown that a diet low in calories and high in fibers affects lipid composition in the rat brain, in a direction opposite to that normally believed to reduce age-related deterioration of brain functions.

Age-related ability of rats kept on a life-long hypocaloric diet in a spatial memory test. Longitudinal observations.

Cognitive behavior was assessed in a test specific for spatial memory, according to a longitudinal experimental model, in populations of 12-, 24- and 30-month-old rats which were fed ad lib either a standard (ST) or a hypocaloric (HY) diet, that had been shown to reduce age-related pathologies and to increase survival. Already at 12 months of age, some cognitive deficits were observed in ST but not in HY rats. When retested 12 and 18 months later, the animals performed better at the beginning of the test than when tested for the first time, indicating that some aspects of previous experience lead to a preservation of spatial memory. Deficits which had been previously observed in 2-year-old groups in a cross-sectional experimental model were not evident this time. Some of the differences between the two diet groups observed 12 months before disappeared. When testing was repeated for the third time at 30 months of age, ST fed rats presented very marked deficits in learning and in memory, which were not seen in the HY group. It thus appears that a dietary regimen in which part of the calorie-rich components, such as lipids and carbohydrates, are replaced with vegetable fibers, retards some of the age-related deteriorations of brain functions.

Org2766 improves performance of rats with unilateral lesions in the fimbria fornix in a spatial learning task

ACTH and related peptides are known for their effects on behavior and for their efficacy on peripheral nerve regeneration. More recently, evidence demonstrating neurotrophic effects of Org2766 on recovery after damage of the central nervous system has become available. Aging studies indicated that particularly the hippocampus appears susceptible to peptide treatment. Therefore, in this study the neurotrophic influence of Org2766 on recovery of hippocampal functioning was studied after transection of the fimbria fornix connection. Analogous to results obtained with recovery of sensorimotor function following peripheral nerve damage a chronic treatment with Org2766 facilitates recovery of the impaired function, i.e. spatial learning in a Morris maze. However, the lesion-induced impairment of avoidance behavior was not influenced by the peptide treatment.

Effects of the active constituents of Crocus Sativus L., crocins, in an animal model of obsessive-compulsive disorder

Crocins are among the active components of the plant Crocus Sativus L. C. Sativus L. and its constituents were effective in different models of psychiatric disorders including anxiety and depression. Obsessive-compulsive disorder (OCD) is a common psychiatric disorder defined by the presence of obsessive thoughts and repetitive compulsive actions. The non selective serotonin (5-HT) receptor agonist mCPP is known to induce OCD-like behavior (excessive self-grooming) in rodents and exacerbate symptoms in patients with OCD. The present study investigated whether or not crocins were able to counteract excessive self-grooming induced by mCPP (0.6 mg/kg, i.p.) in rats. Crocins (30 and 50mg/kg, i.p.) attenuated mCPP-induced excessive self-grooming. The present results also indicate that these effects of crocins on an animal model of OCD cannot be attributed to changes in locomotor activity. Our findings suggest that the active constituents of C. Sativus L. crocins might play a role in compulsive behavior and support a functional interaction between crocins and the serotonergic system.

Effects of the nitric oxide synthase inhibitor L-NAME on recognition and spatial memory deficits produced by different NMDA receptor antagonists in the rat.

There is consistent experimental evidence that noncompetitive antagonists of the N-methyl-D-aspartate (NMDA) receptor, such as ketamine, MK-801, and phencyclidine (PCP), impair cognition and produce psychotomimetic effects in rodents. Nitric oxide (NO) is considered as an intracellular messenger in the brain. The implication of NO in learning and memory is well documented. This study was designed to investigate the ability of the NO synthase inhibitor L-NAME to antagonize recognition and spatial memory deficits produced by the NMDA receptor antagonists, MK-801 and ketamine, in the rat. L-NAME (1–3 mg/kg) counteracted MK-801- (0.1 mg/kg) and ketamine (3 mg/kg)-induced performance impairments in the novel object recognition task. L-NAME (10 mg/kg) attenuated ketamine (15 mg/kg)-induced spatial working memory and retention deficits in the radial water maze paradigm. L-NAME, applied at 3 mg/kg, however, disrupted rodents’ performance in this spatial memory task. The present findings indicate (1) that L-NAME is sensitive to glutamate hypofunction produced by other than PCP NMDA antagonists such as MK-801 and ketamine and (2) that L-NAME alone differentially affects rodents’ spatial memory.

Previous experience facilitates preservation of spatial memory in the senescent rat

In an attempt to evaluate whether previous training antagonizes age-related memory deficits, aged rats with previous training experience were compared with aged and young naive rats in the Morris water maze test. The findings of our study indicate that experience seems to facilitate the preservation of the spatial reference memory for 12 months in the aged rat, whereas senescent naive animals showed the usual age-related memory deficits. However, experience seems task-specific since the same aged rats fail to acquire a new different task.