-
[show abstract]
[hide abstract]
ABSTRACT: Flumazenil might be effective to maintain normal performance in case of an alertness demanding situation directly after taking a hypnotic. However, in case personnel have to be alert during a time of the day that the circadian rhythm is programmed for sleep, the use of wake promoting drugs `night be more efficient. The alertness enhancer caffeine counteracted the sleep deprivation induced decline on the performance and activity. Modafinil even improved the activity. Chronic use of caffeine or modafinil did not negatively affect the performance and the activity during daytime and resulted in comparable effects as after a single use of these compounds. This means that caffeine and modafinil are both effective in reducing the sleep deprivation induced declines in performance. Moreover, the stimulants remain effective when used in combination with a hypnotic and even after chronic use no worsening of day time performance was observed. Modafinil reach its maximum effect 2-4 hours after oral administration indicating that it can only be used in situation in which the operation is planned by forehand. Caffeine, a fast and short acting compound, should be useful for short scenarios. In case long term improved alertness is needed a slow release administration will be needed.
02/2007;
-
[show abstract]
[hide abstract]
ABSTRACT: It was already shown that napping before duty may be a good strategy to prevent performance decline during periods in which the circadian rhythm indicates the need to sleep. However, in a military setting, operational factors may prevent the onset and/or maintenance of restful sleep. In this case the use of hypnotics can be beneficial. Since immediate performance after premature waking can be required in a military setting it is important to choose hypnotics that do not result in so-called post-nap hangovers. In this study, the marmoset monkey model was validated as a model for testing the effects of drugs on performance during time shift work as is the case in many military operations. Subsequently, the effect of hypnotics in the late afternoon on performance during late evening, night and early morning missions was tested. It was proven that the homeostasis in marmoset monkeys after sleep deprivation is similar to the human homeostasis: The sleep intensity after a night of sleep deprivation, which will happen during late night or early morning duty, is increased in the first hours of sleep similar to human. Furthermore, a short nap by these animals before the sleep deprivation period can prevent most detrimental effects on performance and activity, as is the case in humans. Therefore, the marmoset monkey can be considered as a valid model for testing effects of drugs affecting the sleep and alertness behavior.
10/2006;
-
[show abstract]
[hide abstract]
ABSTRACT: Poisoning with the potent nerve agent soman produces a cascade of central nervous system (CNS) effects characterized by severe convulsions and eventually death. In animals that survive a soman intoxication, lesions in the amygdala, piriform cortex, hippocampus and thalamus can be observed. In order to examine the mechanisms involved in the effects of soman and to evaluate possible curative interventions, a series of behavioural, electrophysiological and neuropathological experiments were carried out in the guinea pig using the NMDA antagonist N-[1-(2-thienyl)cyclohexyl] piperidine (TCP) in conjunction with atropine and pyridostigmine. The NMDA antagonist TCP appeared to be very effective in the treatment of casualties who suffered from soman-induced seizures for 30 min: (i)Seizures were arrested within minutes after the TCP injection, confirmed by quantitative electroencephalogram (EEG), after fast Fourier analysis. Three hours after TCP the quantitative EEGs were completely normal in all frequency bands and remained normal during the entire 3-week intoxication period. The power shift to the lower (delta) frequency bands, indicative for neuropathology and found in control animals intoxicated only by soman, was not observed in the soman-TCP group. (ii)The gross neuropathology found in soman control animals within 48 h after soman was prevented in soman-TCP animals and was still absent in 3-week survivors. Instead, ultrastructural changes were observed, indicative of defense mechanisms of the cell against toxic circumstances. (iii)Twenty-four hours after soman, soman-TCP animals were able to perform in the shuttle box and Morris water maze. The beneficial effects of TCP on the performance in these tests during the 3-week intoxication period were very impressive, notwithstanding (minor) deficits in memory and learning. (iv)The increase in excitability after TCP was confirmed by an increase in the acoustic startle response. Taken together, these results confirmed the involvement of NMDA receptors in the maintenance of soman-induced seizures and the development of brain damage. They underline the current hypothesis that cholinergic mechanisms are responsible for eliciting seizure activity after soman and that, most likely, the subsequent recruitment of other excitatory neurotransmitters and loss of inhibitory control are responsible for the maintenance of seizures and the development of subsequent brain damage.
Journal of Applied Toxicology 01/2002; 21 Suppl 1:S57-65. · 2.48 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: A number of neurobehavioral methods have been developed to test behavior in marmoset monkeys. These test systems are (1) the bungalow test, which quantifies spontaneous explorative behavior, (2) the hand-eye coordination test, which tests a learned task of coordinated motor behavior, and (3) the fear-potentiated startle response, which tests and quantifies pathological anxiety manifested by a response of fright. The test systems are extensively discussed, and the value of these test systems is exemplified by applying them to neurological disorders to register disease activity and drug efficacy.
Behavior research methods, instruments, & computers: a journal of the Psychonomic Society, Inc 03/2000; 32(1):173-9.
-
[show abstract]
[hide abstract]
ABSTRACT: Subchronic pretreatment with physostigmine (PHY) (0.0125 mg/kg/h) leading to a blood acetylcholinesterase inhibition of about 30% caused no side effects when applied to marmoset monkeys. This was evident on behavioral parameters and on EEG and cortical visual evoked response. Furthermore, this treatment regime, followed by atropine as postintoxication therapy, protected the marmosets against lethality after a 2 x LD50 dose of soman with negligible postintoxication incapacitation. These findings suggest that a symptom-free pretreatment with subchronic PHY could protect man sufficiently against severe soman intoxication.
Toxicological Sciences 02/2000; 53(1):84-91. · 4.65 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The acoustic startle response is a reflex motor response elicited by a sudden loud sound. In two psychiatric disorders, the startle reflex is altered. Normally, the startle response is decreased appreciably when a low intensity sound stimulus is given shortly before the startle eliciting stimulus. This prepulse inhibition of the startle is nearly absent in patients suffering from schizophrenia. In addition, the startle response is increased during periods of anxiety. In this study, a system is described by which the acoustic startle response in marmoset monkeys may be recorded in a reliable way. In using this system, it could be shown that marmosets possess a pre-pulse inhibition (PPI) of the ASR, similar as in other species. Furthermore, it was shown that a fear potentiation of the startle response may be elicited in the marmoset. Potentially, this system may be used for testing anti-psychotic or anxiolytic activity of drugs in primates. In this study, a series of drugs with a known activity on PPI or fear potentiation of the ASR was tested to validate the system. The effects of Buspiron and Diazepam were tested as examples of drugs with a known anxiolytic effect. In addition, Fluvoxamine and Haloperidol were used in these experiments. Amphetamine, Ketamine and Haloperidol were used as drugs to affect the PPI; in these experiments Diazepam was used as a negative control. These experiments were performed in a randomized, cross-over design. In the fear potentiated startle experiments, four animals were used. They received, following a training period to establish a stable baseline fear potentiation, three dose levels of each of the drugs. In addition, the animals were injected with saline S times spread evenly over the total duration of the experiment to test the stability of the baseline fear potentiation. The four animals used in the PPI group were subjected to a similar dosing schedule.
06/1998;
-
[show abstract]
[hide abstract]
ABSTRACT: The effects of the acetylcholinesterase inhibitor physostigmine (PHY) on the auditory startle reflex in guinea pigs were studied. The dose-response curve of PHY appeared bell shaped, with a maximum effect dose of 0.3 mg/kg. In addition, PHY altered the shape of the startle response. The muscarinic antagonist scopolamine (SCO) increased the startle at PHY doses above 0.3 mg/kg without affecting the PHY-induced shape of the response. The decreasing part of the startle due to PHY could be mimicked by the cholinesterase inhibitor soman in combination with 0.3 mg/kg PHY. It appeared that the decreasing part of the dose-response curve at higher dose levels is caused by the cholinesterase inhibitory action of PHY and, in view of the SCO effect, is mediated by muscarinergic receptors. The increasing part of the curve is probably caused by an agonistic action of PHY on neuronal nicotinergic receptors, because the antagonist mecamylamine (20 mg/kg) antagonized the effects of 0.3 mg/kg PHY both on the deflection and shape of the startle.
Pharmacology Biochemistry and Behavior 01/1998; 58(4):909-13. · 2.53 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The therapeutic efficacy of single or repeated doses of HI-6, together with atropine, against soman poisoning were compared both in guinea pigs and in marmoset monkeys. In addition, the pharmacokinetics of HI-6 were determined after single or repeated injections. Both single and repeated HI-6 injections protected guinea pigs effectively against 2 x LD50 soman. The plasma levels of HI-6 after single HI-6 injection fitted a one-compartment elimination model. The plasma levels of HI-6 following repeated injections were in accordance with those predicted using the data obtained after single HI-6 injection. No evidence was found for any disturbance of the HI-6 elimination in guinea pigs following soman intoxication. Marmosets were intoxicated with 2 x LD50 soman (s.c.), followed after 1 min by i.m. injections of atropine and HI-6. One and 2 h later, four animals received additional HI-6 injections. The pharmacokinetics of HI-6 in plasma, after single and repeated HI-6 injections were similar to those found in the guinea pig. Furthermore, repeated HI-6 injections protected effectively against soman: four out of four animals survived, in fair condition. In contrast, only one out of four animals receiving single HI-6-treatment fully recovered within a few days. Two animals died, the fourth animal survived, but had to be euthanized 3 weeks after intoxication.
Toxicology 10/1996; 112(3):183-94. · 3.68 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: An automated device is described to test the exploratory and motor activity of common marmosets (Callithrix jacchus). The device consists of four boxes interconnected by PVC tubes. The presence of an animal in a box is detected by a photocell. Calibration takes place with an electric model train. Movements of the animal from one box to another are detected by disappearance from one and appearance in another box. The apparatus is linked to a PC. The effects of two doses of methamphetamine and of pentobarbital are shown.
Pharmacology Biochemistry and Behavior 05/1994; 47(4):879-81. · 2.53 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Several earlier studies showed that, in contrast with DFP, repeated injections with soman did not lead to behavioral tolerance in rats. The reason for the difference between the effects of these two organophosphate cholinesterase inhibitors was not clear and a neurophysiological approach was undertaken. Four experiments (A, B, C and D) were carried out, each consisting of three groups of rats, SC injected with saline, DFP (600 micrograms/kg) or soman (60 micrograms/kg) respectively. In Experiment B and D the rats were trained to criterion in a two-way shuttlebox. Thereafter, the animals of Experiment B were fitted with suitable electrodes and two days later their EEGs and visual evoked responses (VERs) were recorded, 1 and 24 h after a single dose of the above-mentioned compounds. In Experiment D the trained animals were subsequently injected 3 times per week for 4 weeks with the same doses and their performance was tested 5 days per week, 1 and 24 h after injection. After those 4 weeks, when the DFP-treated animals had developed behavioral tolerance, electrodes were fitted and EEGs and VERs were recorded after two days, again 1 and 24 h after injection, as in Experiment B. The difference with Experiments A and C was that these animals were not trained. Otherwise, treatment schedules and recording procedures of Experiment A were identical to those of Experiments B and of Experiment C to those of Experiment D. In all cases the EEGs and VERs were recorded from animals slowly walking in a rotating hollow transparent wheel. The results show a similar pattern in all four experiments.(ABSTRACT TRUNCATED AT 250 WORDS)
Pharmacology Biochemistry and Behavior 09/1991; 39(4):851-8. · 2.53 Impact Factor
