Investigation into the age-dependence of release of serotonin and noradrenaline in the rat brain cortex and of autoreceptor-mediated modulation of release

Schlicker, Eberhard; Betz, R.; Göthert, M.

doi:10.1016/0028-3908(89)90172-x

Cited by 30 publications

(8 citation statements)

References 18 publications

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“…In recent years, accumulating data suggest that in such cases there is a combined reduction in the efficacy of several neurotransmitters and that this may better describe the mechanisms underlying the related mnemonic deficiencies (Baker and Reynolds, 1989;Hertz, 1989;Schlicker et al, 1989). The present study further supports such a notion.…”

supporting

confidence: 78%

The effects of serotonin depletion and raphe grafts on hippocampal electrophysiology and behavior

Richter‐Levin

Segal

1991

J. Neurosci.

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The involvement of the serotonergic system in spatial learning and a possible correlation between serotonergic modulation of hippocampal electrical activity and spatial learning were studied in rats. Control, partial septal-lesioned (SL), 5,7-dihydroxytryptamine (5,7-DHT)-injected (DHT), doublelesioned (5,7-DHT and SL; DL), and DL rats that were transplanted with embryonic raphe grafts into the hippocampus (RG) were tested in a spatial task in a water maze and in an active avoidance shuttle-box task. The responses of the dentate gyrus (DG) to perforant-path (PP) stimulation were examined in the same rats, under the following conditions: (1) priming stimulation of the PP (testing feedback inhibition), (2) priming stimulation of the commissural pathway (testing feedforward inhibition), (3) during repeated stimulation of the PP at 7 Hz (frequency potentiation), and (4) following tetanic stimulation [long-term potentiation (LTP)]. DL, but not DHT or SL, treatment severely impaired the performance of rats in both reference-and working-memory tasks in the water maze.This effect was not seen in the shuttle box. The ability of the DG to exhibit LTP, which was reduced in the DHT and SL rats, was apparently similar to controls in the DL group. DL, but not DHT or SL alone, resulted in a reduction of inhibition in the DG. Roth the behavioral deficits and the reduction in hippocampal inhibition were ameliorated by intrahippocampal raphe grafts. These results indicate that the serotonergic innervation of the hippocampus plays a role in spatial learning when the septohippocampal neurotransmission systems are disrupted. Furthermore, these results suggest that restoration of modulation of hippocampal inhibition, by raphe grafts, underlies the behavioral recovery observed in these rats.The hippocampus is involved in learning and memory processes and, in particular, in spatial learning (O'Keefe and Nadel, 1978;Morris et al., 1982;Barnes, 1988;Squire and Zola-Morgan, 1988). Serotonergic fibers, arising from the midbrain raphe (MR) nuclei, densely innervate the hippocampal formation and the dentate gyrus (DG, Azmitia and Segal, 1978; Moore, 198 l), suggesting a role for 5-HT in hippocampal functions. Depletion of forebrain 5-HT, however, has little effect on spatial performance in rats (Asin et al., 1985;Altman et al., 1989; RichterReceived Sept. 26, 1990; revised Dec. 26, 1990; accepted Dec. 28, 1990. We wish to thank H. Markram and M. Wain for valuable comments on the manuscript and Ms. V. Greenberger for help in AChE staining and 'H-imipramine binding. This research was supported by a grant from MINERVA Foundation, Munich, Germany.Correspondence should be addressed to Menahem Segal at the above address. Copyright 0 1991 Society for Neuroscience 0270-6474/91/l 11585-12$03.00/O Levin and Segal, 1989). Recent studies have indicated that, under conditions in which other neurotransmission systems are disrupted, the serotonergic system becomes crucial for correct spatial performance (Vanderwolf, 1987;Nilsson et al., 1988;Richter-Levi...

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confidence: 78%

The effects of serotonin depletion and raphe grafts on hippocampal electrophysiology and behavior

Richter‐Levin

Segal

1991

J. Neurosci.

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“…Investigations on brain slices Cerebral cortex slices (0.3 mm thick, 3 mm in diameter) were prepared from male Wistar rats and from pigs of either sex. The slices were incubated for 60 min in physiological salt solution at 37°C (for composition, see Schlicker et al, 1989a) containing 0.1 UM [3H]-5-HT (12. New England Nuclear,Dreieich,Germany).…”

Section: In Vitro Studiesmentioning

confidence: 99%

Anpirtoline, a novel, highly potent 5‐HT_1B receptor agonist with antinociceptive/antidepressant‐like actions in rodents

Schlicker

Ulrich²,

Hamon

et al. 1992

British J Pharmacology

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3 Like 5-HT, anpirtoline concentration-dependently inhibited forskolin-stimulated adenylate cyclase activity in homogenates from the rat substantia nigra. Both effects were not additive, and could be prevented by 5-HTlB receptor antagonists such as propranolol and penbutolol.4 In superfused rat and pig brain cortex slices preincubated with [3H]-5-HT, the electrically evoked tritium overflow was inhibited by anpirtoline and 5-HT. Whereas 5-HT was equipotent in both tissues (EC50 = 69 nM), anpirtoline was markedly less potent in pig brain cortex slices (EC50 = 1190 nM) than in rat brain cortex slices (EC50 = 55 nM). The concentration-response curve for anpirtoline was shifted to the right by metitepine in both preparations. 5 In the social behaviour deficit test, anpirtoline and trifluoromethylphenyl-piperazine were effective in reversing the isolation-induced impairments in mice, an effect shown only by compounds with agonist properties at the 5-HTIB receptor.6 In the electrostimulated pain test using mice, anpirtoline dose-dependently increased the pain threshold with an ED50 of 0.52mgkg-1, i.p. The antinociceptive activity of anpirtoline was abolished by pretreatment with cyproheptadine or propranolol. 7 In the forced swimming test in rats, anpirtoline induced a dose-related increase in swimming activity. With an ED50 value of 4.6mgkg-1, i.p., anpirtoline was 4 times more potent than the two standard compounds imipramine and desipramine. The decrease of immobility time or the increase of active periods in this model of behavioural despair is suggested to be characteristic of ant-depressant drugs. 8 Anpirtoline exhibits both antinociceptive and antidepressant-like activities in animals. It is probable that anpirtoline elicits these pharmacological effects via its agonist effect on 5-HT1B and 5-HT1A receptors.

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“…Moreover, we have observed reduced hypothalamic NPY release using in vivo push-pull techniques in the aged rat (Morris et al 1997b). Previous studies investigating the effect of ageing on CNS monoaminergic neurotransmission have relied on in vitro techniques measuring [ 3 H]noradrenaline release in rats and humans (McIntosh and Westfall 1987;Schlicker et al 1989;Feuerstein et al 1990;Cerrito et al 1993). Very few investigations have studied the release of endogenous noradrenaline in vitro (Goldman et al 1987;Ciarleglio et al 1993;Fulford and Marsden 1997).…”

Section: J a Hastings · J M Mcclure-sharp · M J Morrismentioning

confidence: 78%

In vitro studies of endogenous noradrenaline and NPY overflow from the rat hypothalamus during maturation and ageing

Hastings

McClure-Sharp

Morris

1998

Naunyn-Schmiedeberg's Arch Pharmacol

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Marked changes in brain monoamine content and NPY content occur during maturation and ageing. Earlier in vivo studies in our laboratory have reported blunted K+ stimulated noradrenaline release and reduced NPY overflow in aged animals using microdialysis and push pull techniques. In this study, in vitro superfusion techniques were established to measure endogenous noradrenaline, NPY, DOPAC and 5-HIAA overflow from the hypothalamus of 1, 5 and 16 month old Sprague-Dawley rats. A period of high K+ (56 mM) stimulation was carried out to elicit maximal release. Basal noradrenaline overflow was similar in all age groups of rats and during K+-induced depolarisation similar 3-4 fold increases were observed. On the other hand, basal and K+ stimulated NPY overflow were significantly greater in the adult rats compared to 1 month and 16 month old rats. Despite differences in absolute NPY overflow, the relative increase over resting was not significantly different across age groups. The molar quantities of hypothalamic NPY overflow at rest and under K+ stimulated conditions were three orders of magnitude lower than noradrenaline. Results of these studies suggest that both NPY and noradrenaline can be released from a similar hypothalamic pool. Basal and K+-evoked DOPAC and 5-HIAA overflow were similar between the 3 age groups. Thus the overflow of hypothalamic noradrenaline, DOPAC and 5-HIAA under in vitro conditions was not altered from 1 to 16 months. In contrast, 5 month old rats had significantly higher NPY overflow than the other age groups (P < 0.05), consistent with a reported decline in NPY content with advanced age. Hypothalamic noradrenaline overflow was not affected by ageing, suggesting that a selective loss of NPY in the arcuo-PVN projection, or other projections to the hypothalamus with ageing may contribute to the reduction in NPY overflow in aged rats.

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Investigation into the age-dependence of release of serotonin and noradrenaline in the rat brain cortex and of autoreceptor-mediated modulation of release

Cited by 30 publications

References 18 publications

The effects of serotonin depletion and raphe grafts on hippocampal electrophysiology and behavior

The effects of serotonin depletion and raphe grafts on hippocampal electrophysiology and behavior

Anpirtoline, a novel, highly potent 5‐HT_1B receptor agonist with antinociceptive/antidepressant‐like actions in rodents

In vitro studies of endogenous noradrenaline and NPY overflow from the rat hypothalamus during maturation and ageing

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Investigation into the age-dependence of release of serotonin and noradrenaline in the rat brain cortex and of autoreceptor-mediated modulation of release

Cited by 30 publications

References 18 publications

The effects of serotonin depletion and raphe grafts on hippocampal electrophysiology and behavior

The effects of serotonin depletion and raphe grafts on hippocampal electrophysiology and behavior

Anpirtoline, a novel, highly potent 5‐HT1B receptor agonist with antinociceptive/antidepressant‐like actions in rodents

In vitro studies of endogenous noradrenaline and NPY overflow from the rat hypothalamus during maturation and ageing

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Anpirtoline, a novel, highly potent 5‐HT_1B receptor agonist with antinociceptive/antidepressant‐like actions in rodents