Biomedical subjects

Gernot Riedel

Publications and source records attributed to Gernot Riedel.

6 recordsLinked to original sources

PubMed2003

Glutamate receptor function in learning and memory.

The contribution of glutamate to synaptic transmission, plasticity and development is well established; current evidence is based on diverse approaches to decipher function and malfunction of this principal transmitter. With respect to learning and memory, we are now able to identify more specifically the role played by the three main glutamate receptor classes in learning and memory: centre stage is clearly the NMDA receptor, with overwhelming evidence proving its involvement in the actual learning process (encoding), throughout the animal kingdom. This is discussed with respect to many different types of learning. Evidence for the contribution of the AMPA receptors (AMPARs) is less clear-cut due to the general problem of specificity: block of AMPARs will shutdown neuronal communication, and this will affect various components essential for learning. Therefore, the role of AMPARs cannot be established in isolation. Problems of interpretation are outlined and a specific involvement of AMPARs in the regulation of neuronal excitation related to learning is proposed. Metabotropic glutamate receptors (mGluRs) may contribute very little to the actual acquisition of new information. However, memory formation appears to require mGluRs, through the modulation of consolidation and/or recall. Overall, mGluR functions seem variable and dependent on brain structure and learning task.

Animals↗

PubMed2002

Effects of delta9-THC and WIN-55,212-2 on place preference in the water maze in rats.

RATIONALE: Cannabinoids such as delta(9)-tetrahydrocannabinol (delta(9)-THC) or WIN-55,212-2 (WIN-2) have psychoactive effects on cognition. As a result, the reinforcing properties of delta(9)-THC or WIN-2 may confound learning and memory tests with false negative results. It therefore seems advisable to assess the reinforcing properties of the drugs in the same behavioural model used for learning experiments. OBJECTIVE: We therefore developed conditioned place preference protocols in the open-field water maze and tested both delta(9)-THC (2 mg/kg) and WIN-2 (1 mg/kg and 3 mg/kg). Given that previous reports on cannabinoids have revealed conflicting data and that this was a novel behavioural test, we also tested the benzodiazepine receptor agonist diazepam (2.5 mg/kg). Some methodical refinements were appropriate in order to determine the behavioural strategy implemented by the animals. METHODS: All animals were injected intraperitoneally 30 min prior to training/testing. In experiment 1, male hooded Lister rats injected with drug were repeatedly placed on the drug-related platform and subsequently tested for place preference. In experiment 2, rats were trained to swim to the drug platform on drug days and to the vehicle platform on vehicle days. A series of probe trials was introduced to delineate what had been learned. Experiment 3 studied the effect of WIN-2 on spatial learning in the water maze. RESULTS: Neither WIN-2 nor delta(9)-THC induced place preference in the water maze. When trained in the swim procedure, however, WIN-2 was neutral, but Delta(9)-THC resulted in place aversion. Conversely, diazepam consistently produced place preference in both procedures. WIN-2 (3 mg/kg), however, produced a small learning deficit in the spatial water maze task. CONCLUSION: It appears that the reinforcing properties of delta(9)-THC and WIN-2 in the doses used here are different, despite them both being agonists at cannabinoid receptors within the central nervous system. The fact that delta(9)-THC may be aversively related to a particular context has implications for previous work reporting deficits in spatial learning.

Animals↗

PubMed2002

Variation of CS salience reveals group II mGluR-dependent and -independent forms of conditioning in the rat.

There is good evidence that metabotropic glutamate receptors (mGluRs) are involved in some types of learning, and we have previously suggested that this involvement may reflect the modulation by mGluRs of the signal-to-noise ratio in neural networks. This hypothesis supposes that unspecific activation of mGluRs increases background noise level, so reducing the effectiveness of behaviourally relevant stimuli as signals in the network. We report here that intraperitoneal (i.p.) injection of 4-aminopyrrolidine-2,4-dicarboxylic acid (APDC), a specific agonist of group II mGluRs, disrupts conditioning to context (but not to cue) using conventional procedures. The hypothesis predicts, however, that the effect of the drug should be counteracted by the use of more salient stimuli, which would provide stronger signals to the network. In accordance with this prediction, we find that increases in the salience of either the CS (context) or the UCS (shock) abolish the drug-induced disruption of conditioning. These results suggest that group II mGluRs modulate neural networks involved in association formation.

Animals↗

PubMed2002

Impairment of contextual fear conditioning in rats by Group I mGluRs: reversal by the nootropic nefiracetam.

The blockade of Group I metabotropic glutamate receptors (mGluRs) may be a potential strategy for prevention therapy of neurotoxicity. We here confirm previous reports that systemic application of the Group I antagonist, 1-aminoindan-1,5-dicarboxylic acid (AIDA), causes amnesia in a contextual fear conditioning paradigm in rats. This deficit was fully reversed by long-term pretreatment with the nootropic nefiracetam, which in fact obtained supranormal performance. Our data suggest that application of Group I antagonists to prevent neurotoxicity, combined with nootropic treatment to prevent cognitive deficits, may be a therapeutic strategy for the development of novel antineurotoxic treatments.

Animals↗

PubMed2002

No spatial working memory deficit in beta-amyloid-exposed rats. A longitudinal study.

Two experiments are described assessing whether long-term intraventricular or intrahippocampal administration of beta-amyloid protein 1-40 (beta A1-40) affects spatial working memory in rats monitored in a longitudinal study using the open-field water maze. A delayed matching-to-position procedure (DMTP) was employed in which platform locations were semi-randomly altered between days but were kept constant over the four trials on each day. Intertrial intervals (ITIs) were either 30 s or 1 h between Trials 1 and 2 (all other intervals = 30 s), with Trial 2 performance being an index for spatial working memory. Animals were trained before and tested repeatedly at various intervals after application of various compounds (see below) in five successive test sessions (TSs). In Experiment 1, beta A1-40 was applied after a challenge with long-term oral exposure to aluminium (Al; as 0.1% sulfate in drinking water). This in itself did not affect spatial working memory at any delay, despite of the more than 6 months of intake. beta A1-40 administered alone via intracerebroventricular (icv) minipumps (20 micrograms in 250 microliters) led to a small increase in latencies to find the platform, which recovered to control levels 3 months after minipumps were exhausted. Application of beta A1-40 in Al-exposed animals led to a subtle and progressive decline in working memory. This deterioration was reversed by the nootropic compound nefiracetam, which had no effect on the Al only group. In Experiment 2, well-trained rats were bilaterally implanted with intra-hippocampal minipumps containing beta A1-40 or reverse sequence beta A40-1. This did not impair spatial working memory in the DMTP task, measured either directly after minipumps were exhausted, or 2 weeks later. When intraperitoneally (i.p.) injected with a low concentration of the muscarinic antagonist scopolamine (0.2 mg/kg), a dose that was not effective alone, animals in the beta A1-40 group were amnesic. These data suggest that intra-hippocampal beta A1-40 administration alters cholinergic transmission, but these alterations may be mild and thus do not lead to obvious working memory deficits in a DMTP task in well-trained animals.

Administration, Oral↗

PubMed2002

Long-term study of chronic oral aluminum exposure and spatial working memory in rats.

The authors report an effort to advance animal models that mimic the cognitive decline of Alzheimer's disease. Rats were trained and repeatedly tested in a spatial delayed matching-to-position paradigm in the water maze, with the location of the submerged platform changing between, but not within, days. After Trial 1 (random search) and intertrial intervals of 30 s or 1 hr, memory was tested in Trial 2. Young rats quickly acquired this task and were repeatedly tested after different intervals over 7 months, with a slight increase in performance toward the end of testing, but no difference in latencies between delays. Oral long-term treatment of 1 group with 0.1% aluminum caused no delay-dependent working memory deficit. This testing protocol may enable between- and within-subject long-term assessment of spatial working memory before and after drug treatment and may prove useful in animal models of progressive cognitive decline.

Administration, Oral↗