Complete recovery of olfactory associative learning by activation of 5-HT4 receptors after dentate granule cell damage in rats.

Bilateral intradentate injections of 3.0microg of colchicine induced a substantial loss of granule cells and damage to the overlying pyramidal cell layer in region CA1 in adult male Long-Evans rats. All rats with such lesions showed a significant associative learning deficit in an olfactory discrimination task, while being unimpaired in the procedural component of this task.

Involvement of the basal cholinergic forebrain in the mediation of general (propofol) anesthesia.

Background: Recent studies have pointed out the involvement of the basal forebrain gamma-aminobutyric acid-mediated system in mediating the effects of general anesthesia. In this study, the authors asked whether the basal forebrain cholinergic system is also involved in mediating the effects of general anesthetics such as propofol.

Methods: Cholinergic lesions were produced by administration of the selective immunotoxin 192 immunoglobulin G-saporin into the lateral ventricles, the medial septum, or the nucleus basalis magnocellularis.

Neuroanatomical and behavioral effects of a novel version of the cholinergic immunotoxin mu p75-saporin in mice.

The selective lesion of basal forebrain cholinergic neurons (BFCNs) is an unestimable tool to study the implication of these neurons in cognition, an interest widely motivated by their degeneration in Alzheimer's disease. Here we evaluated the histochemical and behavioral effects of a selective lesion of BFCNs in C57BL/6J mice treated intracerebroventricularly (ICV) with a novel version of the immunotoxin mu p75-saporin (0.4 mug/mouse).

Combined damage to entorhinal cortex and cholinergic basal forebrain neurons, two early neurodegenerative features accompanying Alzheimer's disease: effects on locomotor activity and memory functions in rats.

In Alzheimer's disease (AD), cognitive decline is linked to cholinergic dysfunctions in the basal forebrain (BF), although the earliest neuronal damage is described in the entorhinal cortex (EC). In rats, selective cholinergic BF lesions or fiber-sparing EC lesions may induce memory deficits, but most often of weak magnitude. This study investigated, in adult rats, the effects on activity and memory of both lesions, alone or in combination, using 192 IgG-saporin (OX7-saporin as a control) and L-N-methyl-D-aspartate to destroy BF and EC neurons, respectively.

MDMA (ecstasy) effects in pubescent rats: Males are more sensitive than females.

In Experiment 1, we assessed the effects of 3,4-methylenedioxymethamphetamine (MDMA) on locomotor activity in pubescent male and female Long-Evans rats. Thirty-nine day old rats were injected ip with 10 mg/kg of MDMA (ambient temperature 25 degrees C) three times at 2 h intervals. Initially, females showed greater locomotor activation by the drug than males, however after the second injection, males showed greater hyperlocomotion.

Locomotor and pyretic effects of MDMA-ethanol associations in rats.

3,4-Methylenedioxymethamphetamine [(MDMA) or ecstasy] is a popular club drug often used in combination with ethanol. In the current study, we investigated the effects of MDMA and ethanol combinations on locomotor activity and body temperature of rats. For four consecutive days, male Long-Evans rats were treated daily with a 10-mg/kg dose of MDMA with or without a 1.

Ethanol, 3,4-methylenedioxymethamphetamine (ecstasy) and their combination: long-term behavioral, neurochemical and neuropharmacological effects in the rat.

This study investigated long-term behavioral, neurochemical, and neuropharmacological effects of ethanol-(+/-)-3,4-methylenedioxymethamphetamine (MDMA, ecstasy) combinations. Over 4 consecutive days, male Long-Evans rats received 1.5 g/kg ethanol and/or 10 mg/kg MDMA, or saline.

No facilitation of amphetamine- or cocaine-induced hyperactivity in adult rats after various 192 IgG-saporin lesions in the basal forebrain.

Lesions of basal forebrain cholinergic neurons by intracerebroventricular (i.c.v.

Modulation of photic resetting in rats by lesions of projections to the suprachiasmatic nuclei expressing p75 neurotrophin receptor.

The suprachiasmatic nuclei of the hypothalamus (SCN) are the site of the master circadian clock in mammals. The SCN clock is mainly entrained by the light-dark cycle. Light information is conveyed from the retina to the SCN through direct, retinohypothalamic fibres.

Intraseptal injection of the 5-HT1A/5-HT7 agonist 8-OH-DPAT and working memory in rats.

Rationale: In rats, 5-HT(1A) receptors are present in the septal region, e.g. on cholinergic neurons of the medial septum, where they might be a substrate for cognitively relevant interactions between cholinergic and serotonergic systems.

Does the release of acetylcholine in septal slices originate from intrinsic cholinergic neurons bearing p75(NTR) receptors? A study using 192 IgG-saporin lesions in rats.

In previous studies electrically-evoked release of acetylcholine in septal slices was demonstrated. The present experiment aimed at verifying if this release involved intrinsic neurons bearing p75(NTR) receptors. Long-Evans rats sustained injections of 192 IgG-saporin into the medial septum/diagonal band of Broca (0.

Transplantation of neurospheres after granule cell lesions in rats: cognitive improvements despite no long-term immunodetection of grafted cells.

EGF-responsive C17 murine-derived neural stem cells (neurospheres) were grafted into the dentate gyrus of adult male rats after dentate granule cells lesions produced by colchicine injections. Behavioural performance was evaluated over two post-grafting periods, using tests sensitive to hippocampal dysfunctions. The first period began 1 month after grafting and testing conducted in the water maze and the radial maze distinguished working- and reference-memory performance.

Effects of septal grafts on acetylcholine release from rat hippocampus after 192 IgG-saporin lesion.

The cholinergic inputs to the rat hippocampus were lesioned by intraseptal injections of 192 IgG-saporin. After 15 days, fetal septal cells were grafted into the hippocampus. Thirteen months later, hippocampal acetylcholine (ACh) release was studied by microdialysis.

Neurotransmitter release and its presynaptic modulation in the rat hippocampus after selective damage to cholinergic or/and serotonergic afferents.

Unlabelled: Male Long-Evans rats sustained injections of 5,7-dihydroxytryptamine (5,7-DHT) into the fimbria-fornix and the cingular bundle or/and intraseptal injections of 192 IgG-saporin to induce serotonergic or/and cholinergic hippocampal denervations; Sham-operated rats served as controls. Four to ten weeks after lesioning, we measured (i). the electrically evoked release of acetylcholine ([3H]ACh), noradrenaline ([3H]NA) and serotonin ([3H]5-HT) in hippocampal slices in the presence of drugs acting on auto- or heteroreceptors, (ii).

5,7-Dihydroxytryptamine lesions enhance and serotonergic grafts normalize the evoked overflow of acetylcholine in rat hippocampal slices.

Adult rats were subjected to intracerebroventricular injections of 5,7-dihydroxytryptamine (5,7-DHT; 150 micro g) and, 15 days later, to intrahippocampal grafts of fetal raphe cell suspensions. About 11 months later, we assessed baseline and electrically evoked release of tritium ([3H]) in hippocampal slices, preloaded with tritiated ([3H])choline or [3H]serotonin (5-HT), in the presence or absence of the 5-HT1B receptor agonist CP-93,129 and the 5-HT receptor antagonist methiothepine. HPLC determinations of monoamine concentrations were also performed.

Raphé grafts and 3,4-diaminopyridine-evoked overflow of serotonin in the rat hippocampus after 5,7-dihydroxytryptamine lesions: evidence for 5-HT1A autoreceptors.

A first experiment verified that the overflow of 5-HT evoked by 75 microM 3,4-diaminopyridine in superfused hippocampal slices was calcium-dependent, tetrodotoxin-sensitive and modulable by drugs acting on 5-HT autoreceptors. Subsequently, the technique was used in rats to investigate the effects of 5,7-dihydroxytryptamine lesions and intrahippocampal serotonergic grafts. The lesions reduced the accumulation (-81%) and relative evoked overflow (-23%; absolute evoked overflow -86%) of [ H]5-HT, but increased the relative baseline overflow (+23%; absolute baseline overflow -78%).

Grafts of fetal septal cells after cholinergic immunotoxic denervation of the hippocampus: a functional dissociation between dorsal and ventral implantation sites.

Three-month-old Long-Evans rats were subjected to intraseptal infusions of 0.8 microg of 192 IgG-saporin followed, 2 weeks later, by intrahippocampal suspension grafts containing fetal cells from the medial septum and the diagonal band of Broca. The suspensions were implanted in the dorsal or the ventral hippocampus.

Selective immunolesions of CH4 cholinergic neurons do not disrupt spatial memory in rats.

Adult male Long-Evans rats were subjected to bilateral lesions of the cholinergic neurons in the nucleus basalis magnocellularis (NBM) by injection of 0.2 or 0.4 microg 192-IgG-saporin in 0.

Effects of 192 IgG-saporin on acetylcholinesterase histochemistry in male and female rats.

Sex hormones may exert neuroprotective effects in various models of brain lesions. Male and female Long-Evans rats were subjected to intracerebroventricular injections of 2 microg 192 IgG-saporin or vehicle. Starting 2 days before surgery, half the male rats were treated with estradiol for 7 days.

5,7-DHT-induced hippocampal 5-HT depletion attenuates behavioural deficits produced by 192 IgG-saporin lesions of septal cholinergic neurons in the rat.

Adult Long-Evans male rats sustained injections of 5,7-dihydroxytryptamine into the fimbria-fornix (2.5 microg/side) and the cingular bundle (1.5 microg/side) and/or to intraseptal injections of 192 IgG-saporin (0.

Combined 192 IgG-saporin and 5,7-dihydroxytryptamine lesions in the male rat brain: a neurochemical and behavioral study.

In a previous experiment [Eur J Neurosci 12 (2000) 79], combined intracerebroventricular injections of 5,7-dihydroxytryptamine (5,7-DHT; 150 microg) and 192 IgG-saporin (2 microg) in female rats produced working memory impairments, which neither single lesion induced. In the present experiment, we report on an identical approach in male rats. Behavioral variables were locomotor activity, T-maze alternation, beam-walking, Morris water-maze (working and reference memory) and radial-maze performances.

Septal grafts and evoked acetylcholine release in the rat hippocampus after 192 IgG-saporin lesions.

Adult rats received intraseptal injections of 192 IgG-saporin and intrahippocampal grafts of septal cells. Between 6 and 10 months later, we assessed baseline and electrically-evoked release of tritium in hippocampal slices preloaded with [(3)H]choline, and the uptake of [(3)H]choline, [(3)H]noradrenaline and [(3)H]serotonin by hippocampal synaptosomes. The lesions reduced the accumulation of [(3)H]choline by approximately 40%, the evoked release of [(3)H]acetylcholine by approximately 90%, and the uptake of [(3)H]choline by synaptosomes by 90% in the dorsal hippocampus, but increased the relative baseline release of [(3)H]choline by +43%, and the synaptosomal uptake of [(3)H]noradrenaline (66%) and [(3)H]serotonin (58%) in the ventral hippocampus.

Central cholinergic depletion induced by 192 IgG-saporin alleviates the sedative effects of propofol in rats.

We examined the effect of central cholinergic depletion on the sedative potency of propofol in rats. Depletion was produced by intracerebroventricular administration of an immunotoxin specific to cholinergic neurones (192 IgG-Saporin; 2 microg). As a result of this lesion, acetylcholine concentration was reduced by about 40% in the frontoparietal cortex and in the hippocampus but was essentially normal in the striatum and cerebellum.

Effects of MDL 73005 on water-maze performances and locomotor activity in scopolamine-treated rats.

The stimulation of 5-HT1A receptors in the raphe or their blockade in the hippocampus can reduce cognitive deficits induced by blockade of muscarinic receptors in the hippocampus. We investigated the effects of MDL 73005 (8-[2-(2,3-dihydro-1,4-benzodioxin-2-ylmethylamino) ethyl]-8-azaspiro[4,5] decane-7,9-dione methyl sulphonate), an agonist at 5-HT1A somatodendritic autoreceptors and an antagonist at postsynaptic 5-HT1A receptors in rats treated systemically with scopolamine. Spatial memory was assessed in a water maze using protocols testing reference and working memory.

Cognitive performances and locomotor activity following dentate granule cell damage in rats: role of lesion extent and type of memory tested.

Intradentate injection of colchicine is one of the techniques used to destroy granule cells. This study compared the behavioral effects of various amounts of colchicine (1.0, 3.