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Biomedical subjects

H Rigter

Publications and source records attributed to H Rigter.

At least 19 recordsLinked to original sources

GABA-B receptor activation and conflict behaviour.

Baclofen and oxazepam enhance extinction of conflict behaviour in the Geller-Seifter test while baclofen and diazepam release punished behaviour in Vogel's conflict test. In order to investigate the possibility that the effect of the selective GABA-B receptor agonist baclofen is mediated indirectly via the GABA-A/benzodiazepine receptor complex, the effect of pretreatment of rats with baclofen on [3H]-diazepam binding to washed and unwashed cortical and cerebellar membranes of rats has been studied. Baclofen pretreatment increased Bmax in washed cerebellar membranes when bicuculline was present in the incubation mixture. No effect was seen in cortical membranes. The present results render it unlikely that the effect of baclofen on extinction of conflict behaviour and punished drinking is mediated via the GABA-A/benzodiazepine receptor complex.

Animals

Pituitary hormones and amnesia.

Pituitary hormones profoundly influence behavior through direct actions on the brain. One of these behavioral effects is the attenuation of experimental amnesia. Traditionally, amnesia is considered as a "loss of memory." Memory comprises at least 2 stages: input (memory consolidation) and output (memory retrieval). Theoretically, disturbance of either aspect of memory may be the cause of amnesia. Also, it is possible that amnesia is based on a factor or factors not related to memory. Data and theories on amnesia in man were reviewed. Some salient features were mentioned: (1) amnesia can be induced by a variety of agents; (2) amnesia covers periods ranging from seconds to years; (3) amnesia gradients can be established; (4) amnesia is to a large extent reversible. From this survey, it seems possible that amnesia is not a homogeneous phenomenon and that even in one person a disturbance of both memory consolidation and memory retrieval may be produced by one and the same event. Animal studies in general have confirmed these conclusions. We have developed an animal model in order to study the effects of pituitary peptides on amnesia. This model is based on CO2-induced amnesia for a one-trial passive avoidance response in rats. This amnesia could be attenuated by treatment with ACTH-analogs 1 hour before the retrieval test. This anti-amnesic effect of ACTH-analogs was not dependent on the nature of the behavioral response or the amnesic treatment. The vasopressin-analog DGLVP similarly exerted an anti-amnesic effect when injected before the retrieval trial. In contrast to ACTH-analogs, however, it also reduced the amnesia when injected before acquisition. These results suggest that amnesia may comprise a "faulty-consolidation" and a "faulty-retrieval" component, which may be amended by different pituitary hormones. The study of the anti-amnesic activity of peptides therefore not only serves to characterize the nature of the behavioral effect of these peptides but may also prove to be helpful of the unraveling of processes involved in amnesia.

Adrenocorticotropic Hormone

Rapid development of tolerance to the hypothermic effect of ethanol in mice.

The hypothermic response to i.p. injection of ethanol (2.0-4.0 g/kg) in mice was found to be attenuated by a single equivalent ethanol injection given 24 hr earlier. The diminished hypothermic response was not an artifact since it could not be attributed to changes in body weight and was independent of familiarity with test environment and procedures. A parallel shift in the dose-response curve was found. It appears, therefore, that the reduced change in body temperature is indicative of tolerance. If the second ethanol injection was given 48 or 72 hr later, tolerance could no longer be seen. With injections spaced 24 hr apart, a third administration of ethanol did not further increase the tolerance seen after the second injection. Since blood ethanol levels did not differ in tolerant and nontolerant mice, and since tolerance was already present 10 min after the second ethanol injection, a functional rather than a metabolic tolerance is likely.

Animals

Attenuation of amnesia in rats by systemically administered enkephalins.

The pentapeptides methionine-enkephalin and leucine-enkephalin are both able to reduce experimentally induced amnesia in rats. In contrast to the possible analgesic activity of these peptides, the anti-amnesic effect is seen after systemic administration of dosages of 30 micrograms or lower. The nature of the anti-amnesic effect is different for the two peptides.

Animals

Parallel changes in behaviour and hippocampal monoamine metabolism in rats after administration of ACTH-analogues.

Application of footshock during the acquisition trial of a one-trial passive avoidance test is associated with a rise in the concentration of serotonin in the hippocampi of rats 24 hr after termination of the acquisition trial. Rats subjected to amnesic treatment with carbon dioxide (CO2) immediately after footshock do not show this rise in the hippocampal concentration of serotonin. The ACTH-analogues, ACTH 4-10 and ACTH 4-10 (7D-Phe), alleviate CO2-induced amnesia for the passive avoidance response when administered 1 hr before retrieval test 24 hr after acquisition. These peptides do not have anti-amnesic activity when given before acquistion. Another ACTH-analogue, ACTH 11-24 does not affect amnesia, given before either the acquisition or the retrieval test. The anti-amnesic effect of ACTH 4-10 AND ACTH 4-10 (7D-Phe), was correlated with a rise in the hippocampal serotonin concentration similar to that observed in non-amnesic animals. Pre-acquisition treatment with ACTH 4-10 or administration of ACTH 11-24 did not affect hippocampal serotonin concentrations. Changes in the hippocampal concentrations of noradrenaline, dopamine, tryptophan and tyrosine were not related to the behavioural activity of any of the peptides. It is suggested that alterations in hippocampal serotonin metabolism 24 hr after acquisition of a passive avoidance response are associated with the retrieveability of the passive avoidance response.

Adrenocorticotropic Hormone

[Possible consequence of ACTH-like peptides for human mental performance (author's transl)].

ACTH affects behavior of rats. The results of the reported experiments suggest that ACTH effects on conditioned behavior are the result of an improved motivation or attention. The ACTH fragments, ACTH 4--10 and ACTH 4--9, have the behavioral effects of ACTH but are devoid of endocrine activities. The ACTH 4--9 analog H-Met(O2)-Glu-His-Phe-D-Lys-Phe-OH (Org 2766) has behavioral activity after oral administration. ACTH-like-peptides restore the behavioral deficiencies of hypophysectomised rats and delay extinction of conditioned behavior of normal rats independent of the type of conditioning. So is extinction of pole jump avoidance and extinction of conditioned tast aversion delayed after Org 2766. Moreover ACTH-like peptides reduce the behavioral deficit in rats with amnesia even when the treatment is given two weeks after the induction of amnesia. In man the administration of a single dose of ACTH 4--10 on Org 2766 reduces the duration of lapses as well as the number of errors of volunteers in a continuous performance task. These and similar observations suggest that ACTH-like peptides may be of practical consequence for the therapy of patients with impairments of cognitive processes.

Adrenocorticotropic Hormone

Parallel changes in behaviour and hippocampal serotonin metabolism in rats following treatment with desglycinamide lysine vasopressin.

Application of a foot shock during the acquisition trial of a one-trial passive avoidance task is associated with a rise in the concentration of serotonin in the hippocampus 24 h after conclusion of the acquisition trial. Carbon dioxide (CO2) induces amnesia for the passive avoidance response when administered immediately upon termination of the acquisition trial. In rats subjected to CO2 treatment following foot shock the rise in hippocampal serotonin is not observed 24 h later. The vasopressin analogue desglycinamide lysine vasopressin attenuates CO2-induced amnesia for the passive avoidance response when given prior to either the acquisition or the retrieval test (24 h after acquisition). This attenuation of the passive avoidance response is associated with a rise in the hippocampal serotonin concentration similar to the one observed in non-amnesic animals. It is suggested that a correlation exists between changes in hippocampal serotonin metabolism and the retrievability of the passive avoidance response.

Amnesia, Retrograde

A new animal model for the prediction of antidepressant activity.

Animal models presently in use for the screening of potential antidepressant drugs yield numerous false positives and false negatives. In search of a more specific model, we have studied the effects of psychotropic compounds on the behavioural changes induced in rats by the removal of the olfactory bulbs. We have observed that subchronic treatment with antidepressants in general reverses the behavioural alterations displayed by bulbectomized rats in tests of conditioned behaviour. The present paper describes a brief test, the so-called anxiosoif test, which may be used to assess the effects of drugs on the behaviour of bulbectomized rats. Removal of the olfactory bulbs leads to increased water intake in the anxiosoif test and to an attenuation of avoidance when the drinking spout is electrified. This latter effect can be reversed by subchronic treatment with the antidepressant drugs amitriptyline and mianserine (Org GB 94). It is suggested that the behavior of bulbectomized rats may be used as a specific tool in the prediction of antidepressant activity of novel compounds.

Animals