Dimebon improves learning in animals with experimental Alzheimer's disease

Systemic administration of antihistamine drug dimebon improves active avoidance conditioning in rats with chronic partial deprivation of cerebral cholinergic functions caused by intracerebroventricular injections of AF64A. The effects of dimebon on learning are similar to those of tacrine used in the treatment of Alzheimer's disease. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 129, No. 6, pp 640–642, June, 2000     

Enhanced inhibitory avoidance learning prevents the memory-impairing effects of post-training hippocampal inactivation

Rats were trained on an inhibitory avoidance task to study the effects of post-training administration of tetrodotoxin (TTX, which temporarily inactivates neural activity) on memory consolidation. During training, independent groups of rats received either a mild foot shock (0.8 mA) or a stronger (1.0 mA) foot shock. TTX was administered bilaterally into the dorsal hippocampus immediately after training, and memory of the task was measured 48 h later. We corroborated the typical amnesic effect of intrahippocampal infusions of TTX in those rats trained with the mild-intensity foot shock. More importantly, with the stronger foot shock, the same treatment was ineffective in producing amnesia. These results suggest that, after an enhanced learning experience, other brain regions are also activated, which may compensate for the amnesic effect of TTX infusions into the hippocampus.Due to an error in the citation line, this revised PDF (published in December 2003) deviates from the printed version, and is the correct and authoritative version of the paper.     

Stress-induced impairment of inhibitory avoidance learning in female neuromedin B receptor-deficient mice

Neuromedin B (NMB) is a mammalian bombesin (BN)-like peptide that exerts its function via the neuromedin B receptor (NMB-R). The NMB/NMB-R system is involved in stress response, and therefore we examined behavioral properties in female mice lacking NMB-R using a restraint-induced stress paradigm. Thirty minutes of restraint in a wire mesh cage constituted a sufficient stress stimulus for mice as evidenced by elevated blood glucose concentrations in stressed wild-type and NMB-R-deficient mice. Using a one-trial passive avoidance test, stressed NMB-R-deficient mice exhibited a marked reduction in memory performance. NMB-R-deficient mice exhibited elevated spontaneous activity in a novel environment compared to non-stressed mutant mice after 30-min stress, and a similar difference was also observed between stressed/non-stressed wild-type mice. An elevated plus maze test showed that the stress stimulus had no effect on anxiety in either wild-type or NMB-R-deficient mice. Furthermore, pain response of wild-type and NMB-R-deficient mice induced by electric foot shock was not affected under either stressed or non-stressed conditions. These results indicate that impaired memory performance in stressed NMB-R-deficient mice is not a consequence of changes in spontaneous activity, anxiety, or pain response, and suggest that the NMB/NMB-R pathway may play a role in regulating the stress response via the neural system that controls learning and memory.     

Shock avoidance conditioning and 3H-leucine uptake in a simple vertebrate system.

Myelencephalic grass frogs were trained to avoid shock to a forelimb, in the paradigm of Horridge. Forty-five min after training, these animals reached the criterion for conditioning faster and with fewer mistakes. Yoked control animals exhibited a slight learning deficit 45 min after receiving unavoidable shocks. Thirty min after training there was no difference in total protein content in the neuraxes of trained and yoked animals, but trained animals incorporated relatively more ³H-leucine into presumptive protein. The incorporated radio-activity was largely confined to the half of the neuraxis ipsilateral to the trained limb, but was not consistently confined to any 1 level of the neuraxis. The simplicity of this behavior and the relatively simple neuronal circuitry mediating it recommend this as a useful vertebrate model system for the study of macromolecular correlates of learning.     

Avoidance conditioning in rats following changes in activity of the noradrenergic and cholinergic systems of the brain

Bilateral coagulation of the ventral noradrenergic pathways of the brain in male rats of the Wistar strain disrupted the conditioned passive avoidance response after unconditioned stimulation with a current of 0.75 mA. Injecting 10 mg/kg galantamine into these rats 20 min before training and increasing the unconditioned stimulus to 3 mA improved subsequent avoidance responses. Injecting galantamine under analogous conditions into normal rats impaired this reaction. Disruption of the conditioned avoidance response following the operation may be due to a change in the intracentral interrelation of the noradrenergic and cholinergic systems of the brain.Translated from Fiziologicheskii Zhurnal SSSR imeni I. M. Sechenova, Vol. 68, No. 3, pp. 297–302, March, 1982.     

A pilot study of the effect of mechanical ventilation and heat exchange on house-dust mites and Der p 1 in New Zealand homes

We have examined the effect of reducing relative humidity (RH), with inbuilt mechanical ventilation and heat-exchange (MVHE) units, on house-dust- mite (HDM) counts and allergen levels, in a pilot study of 10 Wellington dwellings. Recent international prevalence studies in adults and children have confirmed a high prevalence of asthma in New Zealand, Sensitivity to HDM is common among the general population, and HDM is the major allergen associated with asthma. Recent studies of allergen levels have confirmed high concentrations of Der p 1 in the domestic environment. While humidity was significantly reduced in those dwellings fitted with ventilation units, no systematic effect on mites or Der p 1 was observed during the study period. When the reductions in humidity were examined in the context of the time spent below the critical equilibrium humidity (CEH), the intervention led to RH values below the CEH for only 39% of the total of 24-h periods for which measurements were made. Reducing RH by means of MVHE in New Zealand domestic dwellings does not lower humidity sufficiently, or long enough, to have any measurable effect on HDM populations.     

ECS produced disruption or facilitation of discriminated active avoidance performance in rats

Two experiments investigated the effect of electroconvulsive shock on the performance of a one-way active avoidance response. In the first experiment it was found that if the response was learned under scopolamine, ECS given prior to relearning failed to produce a deficit. The second experiment demonstrated that ECS facilitated relearning of a response trained to a low criterion level while it disrupted performance of a response trained to a strict criterion. These results support other indications that Deutsch's memory model has predictive value for proactive effects of ECS on relearning (retrieval).     

Differential role of dopamine in drug- and lithium-conditioned saccharin avoidance

Rats learn to avoid palatable saccharin solutions that predict the systemic administration of reinforcing drugs as well as malaise-inducing lithium chloride (conditioned saccharin avoidance, CSA). In the present study the involvement of dopamine (DA) transmission in the acquisition of morphine, nicotine and lithium-conditioned CSA was investigated in a two-bottle choice paradigm. Nicotine tartrate (0.2 and 0.4 mg/kg s.c.) administered 15 min after saccharin presentation induced CSA, with a maximum effect at 0.4 mg/kg. The DA D1 receptor antagonist, SCH 39166 (0.1 mg/kg s.c.) and the DA D2 receptor antagonist raclopride (0.3 mg/kg s.c.), administered immediately after saccharin, prevented CSA induced by the lower but not by the higher dose of nicotine. However, combined administration of the two antagonists prevented CSA induced by the higher dose of nicotine. SCH 39166 prevented CSA induced by all morphine doses while raclopride prevented only CSA induced by the lowest dose of morphine (1.75 mg/kg). CSA induced by different doses of lithium given by the same schedule of drug-CSA (i.e. two pairings, 15 min after saccharin) was not affected by SCH 39166. However SCH 39166 impaired the acquisition of lithium-CSA when lithium was given 60 min after saccharin. In contrast, raclopride failed to affect lithium-CSA independently from the delay between saccharin and lithium. These results suggest that DA can play different roles in drug- and in lithium-CSA and are consistent with a different mechanism of drug- as compared to lithium-CSA.     

Learning and retention of a shock avoidance task by rat using deafferented hind limb

Learning and retention of a shock avoidance task were studied in the absence of proprioceptive or other topographic feedback. Rats with a deafferented hind limb were trained using the instrumental shock avoidance and retention paradigm of Horridge. Rats received shock whenever they lowered an electrode attached to a deafferented hind foot into an electrolyte bath; yoked-control rats received the shocks to a deafferented hind food along with the experimental animals. Experimental animals consistently held their feet above the electrolyte (p<0.01). During the early minutes of the second phase (a testing situation, in which the experimental and control animals were both shocked for leg lowering) the experimentals received fewer shocks than the controls (p<0.001); the controls eventually withheld their feet (p<0.001). These results indicate that rats with deafferented hind limbs provide a simple system for the study of learning and retention in the absence of proprioceptive or other topographic feedback.     

Pharmacological analysis of pentagastrin-modulated behavior caused by stimulation of the ventromedial hypothalamus

Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 116, N ^o 8, pp. 178–181, August, 1993