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H Van Riezen

Publications and source records attributed to H Van Riezen.

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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

Neuroheptapeptide influence on attention and memory in man.

Twenty normal, male volunteers were administered a subcutaneous injection of either ACTH/MSH 4-10 or diluent and two weeks later received the alternate injection in a complete crossover, double-blind design with order balanced. Subjects were given a battery of psychological tests, including a continuous performance task (CPT), following each injection. Visual evoked responses were recorded during the CPT. Resting, eyes-closed EEGs were also obtained. ACTH/MSH 4-10 improved attention and in so doing improved visual-motor learning and visual, but not verbal, memory, EEG data were consistant with activation of the diffuse thalamic projection system.

Adrenocorticotropic Hormone

Reversal of amnesia by an orally active ACTH 4-9 analog (Org 2766).

The ACTH 4-9 analog, H-Met((O2)-Glu-His-Ph-D-Lys-Phe-OH (Or 2766), attenuates in rats CO2-induced amnesia for a one-trial passive avoidance step-through response when administered prior to the retrieval test but not when given prior to acquisition. Even a dose of 0.001 mug/rat Org 2766 yields an anti-amnesic effect. In this respect Org 2766 is more active than the ACTH fragment ACTH 4-10. An anti-amnesic effect was also obtained when Org 2766 was administered orally. ACTH 4-10 (100 mug/rat) has to be given SC within 8 hr of the retrieval test in order to be effective. A similar time span of effectiveness was observed when Org 2766 was SC injected in a dose of 0.1 mug/rat. The anti-amnesic effect of ACTH 4-10 remains when the time interval between acquisition and retrieval is extended beyond the usual 24 hr. The same appeared to be true for SC ADMINISTERED Org 2766. It is suggested that ACTH-like peptides, and particularly the orally active Org 2766, may be helpful in the treatment of deficient mental performance.

Administration, Oral

Effects of various drugs supposed to interact with serotonin on PGO frequency changes induced by reserpine and 5-hydroxytryptophan.

Reserpine induced ponto-geniculo-occipital (PGO) spikes in the lateral geniculate nucleus. This was used as a model to evaluate the possible anti-reserpine effects of Org GB 94-1,2,3,4,10,14b-hexahydro-2-methyldibenzo[c,f]pyrazino [1,2-alpha]azepine monohydrochloride-methiothepin, imipramine and atropine. In cats, under local anaesthesia, 3.2 mg/kg of methiothepin (a serotonin antagonist and neuroleptic) increased PGO density while 5-hydroxytryptophan (5-HTP) effects were blocked. A dose of 0.32 mg/kg of imipramine or atropine greatly reduced PGO density while potentiating 5-HTP effects. Org GB 94 had no effect in doses up to 10 mg/kg, where a slight decrease of PGO density was found, while 5-HTP effects were unchanged. At 32 mg/kg, EEG was pronouncedly changed by Org GB 94 but only a short-lasting decrease in PGO density was noted. On the basis of these results it seems improbable that the behavioural effects of Org GB 94 are to be explained by the same mechanism (i.e. serotonin uptake inhibition) as that of imipramine.

5-Hydroxytryptophan