Retention Of Passive Avoidance Task Research Articles

Ноотропные и анксиолитические эффекты гептапептида АКТГ 6-9 Pro-Gly-Pro

Melanocortins (MCs) have a wide spectrum of physiological activity. All native MCs have a core pharmacophore structure of tetrapeptide His-Phe-Arg-Trp sequence, corresponding to ACTH6-9 fragment. The sequence is necessary for activation of all subtypes of MC receptors, but the tetrapeptide has poor potency and selectivity. It was shown earlier that the addition of proline-rich sequences to natural peptides led to enhancing and prolongation of their neurotropic effects. An example of such a compound is fragment ACTH4-10 analog with prolong neurotropic effects heptapeptide Semax (ACTH4-7Pro-Gly-Pro). The work is devoted to the research of the effects of a synthetic peptide comprising the natural ACTH6-9 sequence and the fragment PGP in its structure – ACTH6-9PGP (HFRWPGP). The peptide effects on the learning ability and anxiety level were studied in white rats. The peptide was injected intranasally at a dose of 0.05 mg/kg 15 min or 20 h before the experiment. It was shown that heptapeptide ACTH6-9PGP improved the acquisition of food-motivated maze task and retention of passive avoidance task, and also it exhibited an anxiolytic activity in elevated plus maze test when injected 15 min before testing. The peptide administration 20 h before testing did not lead to changes in learning parameters and anxiety level in comparison to control animals. Thus, the peptide the structure of which includes ACTH6-9 fragment and tripeptide PGP has nootropic and anxiolytic activity. Consequently, the spectrum of neurotropic activity of ACTH6-9PGP coincides with the spectrum of Semax activity, but the duration of its effects is much shorter.

Subacute poisoning of mice with deltamethrin produces memory impairment, reduced locomotor activity, liver damage and changes in blood morphology in the mechanism of oxidative stress

BackgroundDeltamethrin (DEL) is a synthetic pyrethroid (PYR) insecticide, potent neurotoxicant. The current investigation was envisaged to explore behavioral, biochemical and morphologic effects of subacute poisoning with DEL in mice and to find one common mechanism of these changes. MethodsMice were daily injected ip with different doses of DEL: 8.3, 20.75 or 41.5mg/kgbw for 28 days. Their memory retention in passive avoidance task (PA), fresh spatial memory in a Y-maze and locomotor activity were measured once weekly. On day 29, blood morphology, alanine transaminase (ALT) activity and creatinine concentration in the blood sera, superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities were measured in the livers and kidneys. Livers were examined with light microscopy. ResultsSignificant impairment of memory retention was recorded on day 2, 7 and 28 after exposure to DEL. Fresh spatial memory was significantly impaired by the highest dose of DEL on day 1, 14 and 28. Locomotor activity was reduced at every stage of experiment in all the groups exposed to DEL. In the animals exposed to the highest dose of DEL activities of alanine transaminase (ALT) and SOD were elevated, GPx was reduced, lymphocyte infiltrates were detected in the livers and there were changes in blood morphology. ConclusionThe results obtained indicate that liver and bone marrow, apart from the central nervous system (CNS) are damaged in the course of subacute poisoning with DEL. The possible common mechanism of the damage is oxidative stress.

Effects of REM sleep deprivation on cholinergic receptor sensitivity and passive avoidance behavior in clomipramine model of depression

This study investigated the effects of REM (rapid eye movement) sleep deprivation (RSD) on the activity of central cholinergic receptors and passive avoidance retention in rats treated neonatally with clomipramine. Male rat pups treated with clomipramine (15 mg/kg, s.c.) twice daily from postnatal day 5 to 21 were subjected to RSD procedure at three months of age, for 4 days consecutively. In the post-RSD phase, RSD-control rats showed a significantly enhanced cholinomimetic-induced hypothermia and an improved retention in passive avoidance task. However, these measures were not significantly different in RSD-experimental group as compared to rats treated neonatally with saline. These results suggest that RSD reverses the sensitivity of central cholinergic receptors in rats given clomipramine neonatally, and this mechanism may be involved in mediating the antidepressant effects of RSD treatment in clomipramine model of depression.

Nociceptin system plays a role in the memory retention: involvement of naloxone benzoylhydrazone binding sites.

We investigated the role of nociceptin system in learning and memory in mice. The deficiency of nociceptin receptors and nociceptin itself did not affect the alternation behavior in the Y-maze test. In the passive avoidance test, the step-through latencies of nociceptin receptor knockout mice were longer than those of wild-type mice. Nociceptin shortened the step-through latency in wild-type mice. This impairment on passive avoidance task was reversed by naloxone benzoylhydrazone (NalBzoH), indicating that the amnesic effects of nociceptin may be mediated through the NalBzoH recognition sites. These suggest that nociceptin system plays an important role in the memory retention of passive avoidance task, and NalBzoH-recognized sites are involved in nociceptin-induced impairment of the memory retention.

Loss of cholinergic neurons in the nucleus basalis induces neocortical electroencephalographic and passive avoidance deficits

The present experiments were designed to examine the hypothesis that the degeneration of cholinergic nucleus basalis is related to the cognitive and neurophysiological deficits found in old age. Aged (26 months) rats were impaired both in the acquisition of spatial (water-maze) task and retention of passive avoidance task. During aging, neocortical electroencephalographic fast activity was decreased and high-voltage spindles increased. Loss of choline acetyltransferase-positive neurons correlated with the high-voltage spindle incidence and passive avoidance retention deficit. Unilateral ibotenate nucleus basalis lesioning decreased choline acetyltransferase activity in the cortex and produced a large nonspecific subcortical cell loss in young rats. Ibotenate-lesioned rats were impaired in spatial learning and passive avoidance retention in young rats. Quisqualic acid produced a greater decrease in cortical choline acetyltransferase activity and smaller nonspecific subcortical cell loss than ibotenate lesioning. Spatial learning was not impaired, but passive avoidance performance was disrupted. Slow waves and high-voltage spindles were increased and beta activity decreased on the side of either quisqualate or ibotenate nucleus basalis lesioning. These results demonstrate that age-related neurophysiological and cognitive deficits result partially from the loss of cholinergic neurons in the nucleus basalis and that quisqualic acid nucleus basalis-lesioning in young rats may be used as a pharmacological model of the age-related cholinergic neuron loss.

Behavioral effects of centrally administered dynorphin and [D-ala 2-D-leu] enkephalin (DADLE) in rats

Dynorphin and [D-ala 2-D-leu] enkephalin (DADLE) were administered directly into the cerebrolateral ventricles of rats and effects on various indices of sensorimotor function and retention of a passive avoidance task were measured. Dynorphin markedly suppressed exploratory motor activity and decreased responsiveness to an acoustic stimulus. Although increases in latency to respond to a noxious thermal stimulus were seen in rats after dynorphin, these changes were always associated with alterations in motor capacity. Injection of dynorphin immediately after a passive avoidance training trial had no significant effect on retention 1 week later. The physiological effects of DADLE were clearly different than those of dynorphin. DADLE produced a biphasic decrease followed by an increase in motor activity and an increased acoustic startle reactivity. DADLE had no effect on reactivity to a noxious thermal stimlulus. Posttrial administration of DADLE significantly impaired retention of a step-through passive avoidance task 1 week after training. These data indicate different neurobiological roles for kappa and delta opiate receptors in the central nervous system.