Pharmacological treatment dose-relatedly improves learning and hippocampal long-term potentiation

Ashton, David; Werbrouck, Leen

doi:10.1016/0006-8993(91)91093-g

Cited by 7 publications

(2 citation statements)

References 15 publications

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“…Active avoidance learning (associative signal-response learning) has been demonstrated to be accompanied by changes in hippocampal long-term potentiation (Ramirez and Carrer 1989;Ashton and Werbrouck 1991). Both active avoidance learning (Archer 1983) and long-term potentiation (Bliss et al 1983) are affected by depletion of NA.…”

Section: Discussionmentioning

confidence: 99%

Comparison of the effects of acute and subchronic administration of atipamezole on reaction to novelty and active avoidance learning in rats

Haapalinna¹,

MacDonald

Viitamaa³

et al. 1999

Naunyn-Schmiedeberg's Arch Pharmacol

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The effects of an alpha2-adrenoceptor antagonist, atipamezole, on exploratory behaviour in a novel environment, spontaneous motor activity and active avoidance learning were studied after acute injection and continuous infusion (0.1 mg/kg h) for 24 h and 6-9 days in rats. The effects of atipamezole on biogenic amines and their main metabolites in brain were studied after an acute injection (0.3 mg/kg s.c.) and continuous infusion (0.1 mg/kg h) for 24 h and 10 days. The level of central alpha2-adrenoceptor antagonism and the drug concentration in blood and in the brain were measured after continuous infusion for 24 h and 10 days. In behavioural tests, atipamezole had no effect on spontaneous motor activity at any of the doses studied. However, after both acute administration and continuous 24-h infusion, atipamezole decreased exploratory behaviour in a staircase test, but no longer after 6 days of continuous infusion. Acute administration of atipamezole impaired performance in active avoidance learning tests causing a learned helplessness-like behaviour. When the training was started after 7 days of continuous infusion, atipamezole significantly improved active avoidance learning. There was a significant increase in the metabolite of noradrenaline (NA), 3-methoxy-4-hydroxyphenylethyleneglycol sulphate (MHPG-SO4), after 24 h but not any longer after 10 days of continuous atipamezole infusion, although the extent of central alpha2-adrenoceptor antagonism was unchanged and the atipamezole concentration present in brain was even elevated at 10 days compared to levels after 24-h infusion. In conclusion, these results reveal that acute and subchronic atipamezole treatments have different and even opposite effects on behaviour in novel, stressful situations. After acute treatment, atipamezole potentiates reaction to novelty and stress, causing a decrease in exploratory activity and impairment in shock avoidance learning. After subchronic treatment, there was no longer any effect on exploratory behaviour and, in fact, there was an improvement in the learning of a mildly stressful active avoidance test. The changes in behaviour occurred in parallel with attenuation in the MHPG-SO4-increasing effect, thus the suppressed behaviour in the present test conditions after acute atipamezole injection is associated with a major increase in central NA release. The results support the role of alpha2-adrenoceptors and noradrenergic system in reactions both to novelty and stress and have possible implications in cognitive functions as well as in depression.

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Section: Discussionmentioning

confidence: 99%

Comparison of the effects of acute and subchronic administration of atipamezole on reaction to novelty and active avoidance learning in rats

Haapalinna¹,

MacDonald

Viitamaa³

et al. 1999

Naunyn-Schmiedeberg's Arch Pharmacol

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“…in the subgroup with the lowest scores on baseline memo ry tests [7], This suggests that sabeluzole does not improve memory function per se, but reactivates or restores im-paired function. Although the cerebral working mecha nisms of sabeluzole are not yet completely understood, its improvement of fast axonal transport [8] and its effect on voltage-dependent outward K + currents [9] may be impli cated in the effects on memory [10].…”

Section: Introductionmentioning

confidence: 99%

Effect of Sabeluzole (R 58 735) on Memory Functions in Patients with Epilepsy

Aldenkamp

Overweg²,

Smakman

et al. 1995

Neuropsychobiology

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Sabeluzole, a new benzothiazol derivative, has shown positive effects on memory function in animals and in normal volunteers. The present study reports the results of sabeluzole, in memory-impaired patients with localization-related (partial) epilepsy. A randomized, double-blind placebo-controlled parallel-group design was used. A total of 38 patients entered a prospective baseline. Five patients dropped out from the study, thus 33 patients were randomly assigned to either a 12-weeks treatment with sabeluzole (n = 14) or placebo (n = 19). The treatment phase was preceded by a titration phase of 4 weeks to obtain serum levels of sabeluzole between 50 and 130 ng/ml. In order to maintain blindness, a sham titration was carried out in the placebo group. The number of ‘responders’, i.e. patients with a > 1 SD improvement on at least three of the memory tests was 9 out of 14 (64.3%) in the sabeluzole group and 7 out of 19 (36.8%) in the placebo group. This suggests a clinically relevant effect of sabeluzole. The analysis of the memory tests showed a statistically significant improvement with sabeluzole on the verbal long-term memory test. This could represent a specific drug effect and is in line with previous results of normal volunteer studies that also found improvement mainly restricted to the area of verbal long-term memory.

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