Biomedical subjects

Trevor Archer

Publications and source records attributed to Trevor Archer.

At least 19 recordsLinked to original sources

PubMed2006

Remission and cognitive ability in a cohort of patients with schizophrenia.

INTRODUCTION: Patients with schizophrenia were studied regarding their ability of achieving symptomatic remission. It was found that only approximately one-third of the patients fulfilled the criteria for remission. The importance of cognitive performance was studied to decide whether cognitive ability is a contributing factor for achieving remission. MATERIALS AND METHODS: A homogeneous cohort of 211 patients, of whom 76 patients attained remission (36%), and 135 patients (64%) failed to, was studied. Remission was decided by the use of eight items from the PANSS in which none of these items should have a score above three points. The patients were also tested on a comprehensive battery of cognitive tests including vigilance, working memory, long-term memory, executive functioning, learning performance, visuomotor speed/efficacy, cognitive flexibility and pre-morbid functioning. RESULTS: Marked differences were exhibited in the cognitive abilities in all domains of patients who had attained remission in comparison with those who had not. DISCUSSION: This study highlights the importance of cognitive performance as one possible predictor of remission. Patients without remission had lower cognitive ability and may have more difficulty in benefiting from, or complying with their treatment. As a consequence, various forms of supportive treatment might increase the likelihood of remission.

Adult↗

PubMed2006

Phencyclidine affects memory in a nitric oxide-dependent manner: working and reference memory.

Phencyclidine (PCP), a non-competitive NMDA receptor antagonist, was used to model schizophrenia-like cognitive dysfunctions of learning and memory in rats using the Morris water maze model for spatial memory. A protocol introduced by Baldi and co-workers was used to distinguish working memory from reference memory. Male Sprague-Dawley rats were administered PCP (2.0 mg/kg) before the first swimming trial on each of five spatial memory acquisition days, either alone or after pre-treatment with the nitric oxide synthase inhibitor, L-NAME (10 mg/kg). Probe tests for memory were conducted before and after each acquisition session. The results showed that PCP disrupted the acquisition of both working and reference memory. Pre-treatment with L-NAME reversed both these effects of PCP. L-NAME treatment by itself did not significantly alter either acquisition or retention of spatial memory.

Analysis of Variance↗

PubMed2006

Effects of phencyclidine on spatial learning and memory: nitric oxide-dependent mechanisms.

Cognitive deficits of schizophrenia constitute a disabling part of the disease predicting treatment success as well as functional outcome. Phencyclidine (PCP), a non-competitive NMDA receptor antagonist was used to model schizophrenic cognitive dysfunctions of learning and memory using the Morris water maze paradigm for reference memory. In experiment 1 male Sprauge-Dawley rats were acutely administered PCP (0.5, 1.0 and 2.0 mg/kg s.c.) before the first swim session on each of the four acquisition days. Probe test for reference memory was performed 2 days after the last acquisition day; the first probe without drug treatment to assess reference memory and a second probe with prior drug treatment to control for state dependency effects of PCP. In experiment 2 the effects of pre-treatment (10 min before PCP) with the nitric oxide synthase inhibitor, L-NAME (10 mg/kg s.c.), on the PCP (2 mg/kg)-induced spatial memory deficit was evaluated in the Morris water maze paradigm for reference memory. The results showed that PCP in a dose of 2 mg/kg disrupts spatial learning as estimated by prolonged search time to find platform during acquisition as well as the reference memory test as measured by less time spent in target quadrant during probe trial. No state dependency effects of PCP were found. Pre-treatment with L-NAME completely reversed the PCP-induced disruption of acquisition learning. The reference memory disruption was, however, not completely restored as measured by probe trial.

Analysis of Variance↗

PubMed2006

Subchronic administration of haloperidol influences the functional deficits of postnatal iron administration in mice.

C57/BL6 mice were administered either 7.5 mg Fe (II)/ kg or vehicle (saline) postnatally on Days 10-12 after birth. From 64 days of age onwards for 24 days, groups of mice were administered either haloperidol (0.25 or 1 or 2 mg/kg, s.c.) or vehicle (Tween-80). Twenty-four hours after the final injection of either neuroleptic compound or vehicle, spontaneous motor activity was measured over a 60-min interval. Postnatal Fe (II)-treatment (7.5 mg/kg, postnatally) reduced motor activity parameters during the initial 20-min periods (0-20 and 20-40 min) and then induced hyperactivity during the final 20-min period over all three parameters of activity, confirming previous observations. Subchronic administration of haloperidol, at the 1 and 2 mg/kg doses, and to a lesser extent the 0.25 mg/kg dose, increased the levels of activity in all three motor activity parameters in postnatal iron-treated mice: locomotion (1st and 2nd 20 min periods), rearing (1st and 2nd 20 min periods) and total activity (1st 20 min period). All three doses of haloperidol abolished the later hyperactivity in iron-treated mice, with the exception of the 0.25 mg/kg dose with regard to rearing behaviour. Apomorphine (1 mg/kg, s.c.) -induced activity was elevated by postnatal iron administration and by subchronic administration of apomorphine at the higher dose levels. In the context of these and other observations, it is suggested that subchronic administration of haloperidol interacting with postnatal iron induces different expressions of dopamine neuron comorbidity underlying movement disorder.

Animals↗

PubMed2005

Antagonism of the nitric oxide synthase inhibitor, L-NAME, of the effects of phencyclidine on latent inhibition in taste aversion conditioning.

Latent inhibition (LI) is a behavioural procedure used to evaluate the potential propsychotic and antipsychotic properties of psychoactive drugs. In the present study, a conditioned taste aversion (CTA) procedure was used to investigate the effects of the nitric oxide (NO) synthase inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME), and the psychotomimetic drugs, phencyclidine (PCP) and d-amphetamine (d-AMP) on LI. PCP (2 mg/kg) and d-AMP (0.5 mg/kg) were both found to enhance LI in this procedure. The effect of d-AMP on LI was less pronounced and this drug also caused a weak disruption of taste aversion conditioning. Pretreatment with L-NAME (10 mg/kg) blocked the LI enhancing effect of PCP on LI but not that of d-AMP. L-NAME by itself caused an attenuation of LI. L-NAME has been shown to block also other behavioural and biochemical effects of PCP in previous studies and these results and the present findings suggest that at least some of the effects PCP are dependent on NO and possibly also that some NOS inhibitors may exert antipsychotic properties.

Analysis of Variance↗

PubMed2005

The effects of phencyclidine on latent inhibition in taste aversion conditioning: differential effects of preexposure and conditioning.

Latent inhibition (LI) is a behavioural procedure in which preexposure to a stimulus not followed by reinforcement retards subsequent conditioning to this stimulus when it is paired with reinforcement. Changes in LI thus reflect greater or lesser retardation of learning which essentially implies a potentiation or an attenuation of the LI effect. LI has proved sensitive to psychotomimetic and antipsychotic treatment, which has encouraged its use to model learning and attention deficits in schizophrenia. In the present study, experiments were conducted to evaluate the effects of the psychotomimetic drug, phencyclidine (PCP, 2 mg/kg), and compare it with D-amphetamine (D-AMP, 0.33 and 1 mg/kg), on LI using a conditioned taste aversion procedure. PCP was found to potentiate LI when administered acutely prior to the conditioning trails, while no such effect was observed when administered prior to the preexposure trials. D-AMP, on the other hand, disrupted LI possibly due to a failure to induce a persistent taste aversion conditioning.

Analysis of Variance↗

PubMed2004

Neurofunctional deficits and potentiated apoptosis by neonatal NMDA antagonist administration.

The early postnatal brain development, when many potentially sensitive processes occur, has been shown to be vulnerable to different pharmacological and environmental compounds. In the present investigation, four groups of neonatal NMRI male mice were administered the glutamate NMDA receptor antagonist ketamine (50 mg/kg, s.c.), or the GABA(A) receptor agonist diazepam (5 mg/kg, s.c.), or co-administered ketamine (50 mg/kg, s.c.) and diazepam (5 mg/kg, s.c.), or vehicle (0.9% saline, s.c.) on day 10 after birth. On day 11, mice from each treatment group were sacrificed and brains were taken for analysis of neuronal cell degeneration, using Fluoro-Jade staining technique. Ketamine, but not diazepam, induced a severe degeneration of cells in the parietal cortex. The opposite was observed for diazepam in the laterodorsal thalamus. The most pronounced cell degeneration was seen in parietal cortex of mice exposed to both ketamine and diazepam. At 2 months of age each treatment group was tested for motor activity and learning performance. Ketamine and ketamine + diazepam treated mice displayed severe deficits of habituation to the test chamber in the spontaneous motor activity test, marked deficits of acquisition learning and retention memory in the radial arm maze-learning task and less shift learning in the circular swim maze-learning task. This study indicates that the observed functional deficits can be related to cell degeneration induced during a critical stage of neonatal brain development. The potentiated apoptosis induced by ketamine and diazepam may have implications for the selection of drugs used in neonatal paediatric anaesthesia.

Animals↗

PubMed2004

Gene-environment interplay in neurogenesis and neurodegeneration.

Factors associated with predisposition and vulnerability to neurodegenerative disorders may be described usefully within the context of gene-environment interplay. There are many identified genetic determinants for so-called genetic disorders, and it is possible to duplicate many elements of recognized human neurodegenerative disorders in either knock-in or knock-out mice. However, there are similarly, many identifiable environmental influences on outcomes of the genetic defects; and the course of a progressive neurodegenerative disorder can be greatly modified by environmental elements. Constituent cellular defense mechanisms responsive to the challenge of increased reactive oxygen species represent only one crossroad whereby environment can influence genetic predisposition. In this paper we highlight some of the major neurodegenerative disorders and discuss possible links of gene-environment interplay. The process of adult neurogenesis in brain is also presented as an additional element that influences gene-environment interplay. And the so-called priming processes (i.e., production of receptor supersensitization by repeated drug dosing), is introduced as yet another process that influences how genes and environment ultimately and co-dependently govern behavioral ontogeny and outcome. In studies attributing the influence of genetic alteration on behavioral phenotypy, it is essential to carefully control environmental influences.

Alzheimer Disease↗

PubMed2004

Neurobehavioural deficits associated with apoptotic neurodegeneration and vulnerability for ADHD.

Several studies involving postnatal administration of the N-methyl-D-aspartate (NMDA) antagonists, dizocilpine (MK-801; 3 x 0.5 mg/kg, at 08.00, 16.00 and 24.00 h) on Postnatal day 11, or Ketamine (1 x 50 mg/kg) or Ethanol (1 x 2.5 g/kg, Ethanol-Low, or 2 x 2.5 g/kg, 2-h interval, Ethanol-High) on Postnatal day 10, are described. Some mice from each treatment/vehicle group were sacrificed 24 h after NMDA antagonist treatment and brain regions were taken for fluoro-jade staining analysis. Functional analysis was initiated at 60 days of age. All three treatments inducing an antagonistic action at NMDA receptors, MK-801, Ketamine and Ethanol-High induced a similar pattern of initial hypoactivity followed by marked and lasting hyperactivity in the motor activity test chambers. In each case, the basal hyperactivity level was abolished by acute treatment with a low dose of D-amphetamine (0.25 mg/kg). All three treatments, MK-801, Ketamine and Ethanol-High, induced a deficit in acquisitive performance in the radial arm maze test of instrumental learning. The deficit induced by postnatal MK-801 was abolished by acute treatment with the low dose of D-amphetamine. All three treatments, MK-801, Ketamine and Ethanol-High, resulted in normal acquisitive performance during the first three test days in the circular swim with the submerged platform maintained in a constant position, but on the fourth test day, with the platform position shifted to a different "quadrant", induced marked deficits. Fluoro-jade staining analyses indicated a devastating cell degeneration in several brain regions of mice administered NMDA antagonists postnatally, including the hippocampus, frontal cortex, parietal cortex, and cerebellum. Severe cell degeneration in the laterodorsal thalamus due to Ethanol or diazepam (5 mg/kg) appeared not to affect the different aspects of function. The pattern of dysfunctional outcome and apoptotic cell loss following postnatal NMDA antagonist treatment offers a plausible similarity to the major aspects of 'syndromatic continuity' in ADHD, hyperactivity, inattention and impulsivity, thereby providing an interesting animal model of the disorder.

Animals↗

PubMed2004

Gene-environment interplay in schizopsychotic disorders.

Genetic studies have sought to identify subtypes or endophenotypes of schizophrenia in an effort to improve the reliability of findings. A number of chromosomal regions or genes have now been shown to have had replicated linkage to schizophrenia susceptibility. Molecules involved in neurodevelopment or neurotransmitter function are coded by many of the genes that have been implicated in schizophrenia. Studies of neurotransmitter function have identified, among others, a possible role for GABA, glutamate and dopamine in animal models of schizophrenia. GABA neurons that co-express the calcium binding protein parvalbumin have been implicated as have glutamatergic metabotropic receptors and dopamine D3 receptors. Stress influences glutamate and dopamine providing another environmental factor that may interact with the influence of genes on neurotransmitter function. Neurotransmitter interactions include influences on signaling molecules and these too have been implicated in forms of learning thought to be affected in schizophrenia. Results continue to unravel the interplay of genes and environment in the etiology of schizophrenia and other psychotic disorders.

Animals↗

PubMed2004

Adolescents' fire-setting awareness under boredom: relation to personality variables.

The present study assessed whether or not there is a relation between fire-setting and boredom. 56 Swedish secondary-school students, 28 adolescent boys and 28 adolescent girls, were randomly assigned to a Control group and an Experimental [Boredom] group divided equally by sex. Participants were required to complete a projective test, a short story the content of which depicted a bored individual fingering a box of matches or lighter and with a bus ticket in his pocket. The Experimental [Boredom] group completed a 15-min. "boredom" test before anticipating the fictional narrative, while the Control group participated in relaxing activities. Two mutually independent judges evaluated the written stories from three standpoints: the number of fictitious fires, the relation to fire, and the boredom in the written stories. The results indicated a significant difference between the Experimental [Boredom] group and the Control group concerning relation to fire.

Adolescent↗

PubMed2003

Effect of postnatal iron administration on MPTP-induced behavioral deficits and neurotoxicity: behavioral enhancement by L-Dopa-MK-801 co-administration.

Two experiments were performed to investigate the interactive effects of postnatal iron administration and adult MPTP treatment upon the function of C57 Bl/6 mice tested at adult age and to ascertain the possible ameliatory effects of a subthreshold dose of L-Dopa co-administered with different doses of the uncompetitive glutamate antagonist, MK-801. Experiment I indicated that postnatal iron induced marked deficits (hypoactivity), initially, in all three parameters of motor activity at the 5.0 and 7.5 mg/kg doses, and to a lesser extent at the 2.5 mg/kg dose. Later combination with MPTP (2x40 mg/kg) potentiated severely these deficits. During the final period of testing a marked hyperactivity was obtained for the two higher dose groups; this effect was abolished in mice administered MPTP. Experiment II indicated that the deficits in motor activity parameters induced by postnatal iron at 7.5 mg/kg were alleviated in a dose-related manner by the co-administration of the uncompetitive glutamate antagonist, MK-801, with a subthreshold dose of L-Dopa. Postnatal iron (7.5 mg/kg) administration followed by low doses of MPTP (2x20 mg/kg) 3 months later virtually abolished all motor activity. The combination of these compounds increased also the motor activity of mice treated with MPTP (2x20 mg/kg) or mice treated with the combination of postnatal iron and MPTP. The combination of MK-801 with L-Dopa increased locomotor (0.3 mg/kg), rearing (0.1 and 0.3 mg/kg) and total activity (0.3 mg/kg) of iron-treated mice during the initial, hypoactive 30-min period of testing. Locomotor activity (0.1 mg/kg) of MPTP-treated mice was increased too during this period. During the final 30-min period of testing all three parameters of activity (locomotion, 0.3 mg/kg; rearing and total activity, 0.1 and 0.3 mg/kg) were enhanced in the iron-treated mice, locomotion (0.1 mg/kg) and rearing (0.1 mg/kg) in the iron plus MPTP treated mice and only locomotion (0.1 mg/kg) in the MPTP-treated mice. In control mice (vehicle+saline), the higher doses of MK-801 (0.1 and 0.3 mg/kg) enhanced both locomotor and total activity. Analyses of total iron concentration in the frontal cortex and basal ganglia of Fe(2+) and vehicle treated mice indicated that marked elevations basal ganglia iron levels of the 5.0 and 7.5 mg/kg groups, later injected either saline or MPTP, were obtained (Experiment I). In Experiment II, iron concentrations in the basal ganglia were elevated in both the Fe(2+)-sal and Fe(2+)-MPTP groups to 170 and 177% of Veh.-sal values, respectively. There was a significant increase in the frontal cortex of iron-treated mice later administered either saline or MPTP (2x40 mg/kg) in Experiment I as well as in those given iron followed by MPTP (2x20mg/kg) in Experiment II. The implications of iron overload in parkinsonism seem confirmed by the interactive effects of postnatal administration of the metal followed by adult MPTP treatment upon motor activity and the activity-enhancing effects of co-administration of L-Dopa with MK-801.

Animals↗

PubMed2003

Hyperactivity following postnatal NMDA antagonist treatment: reversal by D-amphetamine.

Three experiments were performed to study the effects of neonatal administration of glutamate receptor antagonists, on either Day 11 (dizocilpine = MK-801, 3 x 0.5 mg/kg, s.c., injected at 0800, 1600 and 2400 h) or Day 10 (Ketamine, 1 x 50 mg/kg, s.c., or Ethanol-Low, 1 x 2.5 mg/kg, or, Ethanol-High, 2 x 2.5 mg/kg, s.c., with 2-h interval) to male mice pups, on spontaneous motor behavior, habituation to a novel situation and D-amphetamine-induced activity in the adult animals. Mice administered MK-801 showed initial hypoactivity followed by hyperactivity over the later (20-40 and 40-60 min) periods of testing. Mice administered Ketamine and Ethanol-High similarly displayed an initial hypoactivity followed by hyperactivity over the later time (20-60 min) of testing. Habituation to the novel activity test chambers was reduced drastically in the MK-801 mice compared with vehicle-treated mice. Similarly, mice administered Ketamine and Ethanol-High displayed too drastically reduced habituation behavior. The low dose of D-amphetamine (0.25 mg/kg) reduced the hyperactivity of neonatal MK-801-treated mice, particularly from 30-60 min onwards, and elevated the activity level of the vehicle-treated mice. Similarly, the low dose of D-amphetamine (0.25 mg/kg) reduced the hyperactivity of neonatally Ketamine-treated and Ethanol-High-treated mice, particularly from 30-60 min onwards, and elevated the activity level of the respective vehicle-treated mice. Fluoro-jade staining per mm(2) regional brain tissue of MK-801 mice pups expressed as percent of vehicle mice pups showed also that the extensiveness of staining was markedly greater in the parietal cortex, hippocampus, frontal cortex, and lesser so in the laterodorsal thalamus. Ketamine-treated mice showed cell degeneration mainly in the parietal cortex, whereas the Ethanol-High mice showed marked cell degeneration in both the parietal and laterodorsal cortex. The present findings that encompass a pattern of regional neuronal degeneration, disruptions of spontaneous motor activity, habituation deficits and reversal of hyperactivity by a low dose of D-amphetamine suggest a model of Attention Deficit Hyperactivity Disorder that underlines the intimate role of N-methyl-D-aspartate (NMDA) receptors in the developing brain.

Animals↗

PubMed2003

Effects of acute administration of DA agonists on locomotor activity: MPTP versus neonatal intracerebroventricular 6-OHDA treatment.

The effects of several dopamine (DA) receptor agonists upon locomotor activity on adult MPTP-treated mice and postnatal 6-hydroxydopamine- (6-OHDA-) treated rats were assessed in ten experiments. C57 BL/6 mice were administered 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 2 x 40 mg/kg, s.c., 24-hr interval between injections) at 5-months-age, while 1-day-old male Wistar rat pups were given intracisternal 6-OHDA (50 mg, once following desipramine, 25 mg/kg). MPTP-treated mice were tested 4-5 weeks following MPTP injections whereas neonatal 6-OHDA rats were tested at 3-months-age. Locomotor activity was measured in respective activity test chambers following acute administration of DA receptor agonists. In MPTP-treated mice, apomorphine failed to elevate locomotor activity but instead further exacerbated (1.0 and 3.0 mg/kg, s.c.) the hypokinesia of these animals while inducing marked increases in control mice. Cabergoline (0.3 mg/kg, s.c.) and bromocriptine (3.0 mg/kg, s.c.) caused dose-specific elevations of locomotion in MPTP and control mice but suppressed activity at the highest doses. Quinpirole (0.2 mg/kg) and 7-hydroxydipropylaminotetralin (7-OH-DPAT; 300 nmole/kg) increased locomotion in hypokinesic MPTP-treated mice; in control mice, activity was elevated by quinpirole (0.2 and 0.7 mg/kg) and 7-OH-DPAT (100 and 300 nmole/kg), while higher doses suppressed activity. Neither SKF 38393 (1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine-7,8-diol) nor FCE 23884 [4-(9,10-didehydro-6-methylergolin-8 beta-yl) methyl-piperazine-2,6-dione] affected locomotor activity. Apomorphine (0.3, 1.0 and 2.0 mg/kg), bromocriptine (3.0 mg/kg) and cabergoline (1.0 mg/kg) stimulated locomotion in sham-operated rats, and to a greater extent in the 6-OHDA-treated rats. Higher dose cabergoline (3.0 mg/kg) induced increased activity of similar extent in sham controls and 6-OHDA treated rats. Activity-enhancing effects of quinpirole (0.2, 0.7 and 2.1 mg/kg) in sham rats were attenuated in 6-OHDA treated rats. Both SKF 38393 (10 mg/kg) and FCE 23884 (0.3 and 1.0 mg/kg) induced locomotor activity increases in 6-OHDA, but not sham, rats. Finally, 7-OH-DPAT (1200 mg/kg) enhanced activity in 6-OHDA rats vs. shams. The effects of the DA agonists are discussed with regard to the putative antihypokinesic effects in MPTP mice and DA-receptor supersensitivity effects in neonatal 6-OHDA rats, pertaining to their more-or-less selective subreceptor profiles.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

PubMed2002

Neurodevelopmental liabilities of substance abuse.

The perinate is particularly risk-prone to chemical species which have the potential of inducing neuronal apoptosis or necrosis and thereby adversely altering development of the brain, to produce life-long functional and behavioral deficits. This paper is an overview for many substances of abuse, but the purview is much more broadened by the realization that even elevated levels of estrogens and corticosteroids in the pregnant mother can act as neuroteratogens, by passing via the placenta and altering neural development or inducing apoptosis in the perinate. Finally, therapeutic risks of anesthetics are highlighted, as these too induce neuronal apoptosis in the neonate by either blocking N-methyl-D-aspartate receptors or by acting as gamma-aminobutyric acid agonists. By understanding the mechanisms involved it may ultimately be possible to interrupt the mechanistic scheme and thereby prevent neuroteratological processes.

Journal Article↗

PubMed2002

Neonatal 6-hydroxydopamine-induced hypo/hyperactivity: blockade by dopamine reuptake inhibitors and effect of acute D-amphetamine.

Five experiments were performed to assess the changes in motor activity resulting from neonatal administration of 6-hydroxydopamine (6-OHDA) on Days 1 or 2 postnatal, at doses of either 75 or 100 micro g in a volume of 10 micro l vehicle, following pretreatment with either GBR 12909 (40 mg/kg, s.c.) or amphonelic acid (4.0 mg/kg, s.c.) or saline. Motor activity was measured either over 60-min test periods on five consecutive days of testing or at 12-min intervals within a single 60-min test session. The initial extent of locomotor hyperactivity was dependent upon the neonatal dose of 6-OHDA: the 100 micro g, but not 75 micro g, dose induced marked hyperactivity from test day 1 onwards whereas the 75 micro g dose did so from test day 3 onwards. The initial hypoactivity for rearing behaviour was observed for both doses of 6-OHDA: this hypoactivity was altered over successive test days so that by test day 5 an hyperactivity by the 75 micro g, but not 100 micro g, was observed. Pretreatment with either GBR 12909 or amphonelic acid abolished the effects of both doses of 6-OHDA. In the within-60-min test session procedure, 6-OHDA treated rats (both 75 and 100 micro g) showed initial hyperactivity for locomotion that intensified, in relation to the other groups, over each 12-min interval and initial hypoactivity for rearing that developed into hyperactivity over each 12-min interval. Pretreatment with either GBR 12909 or amphonelic acid again abolished the effects of both doses of 6-OHDA. Habituation quotients derived in each case for both procedures indicated severe habituation deficits by 6-OHDA (75 and 100 micro g) rats, compared to the control groups in all four experiments. In Experiment V, a low dose of D-amphetamine abolished the hyperactivity of 6-OHDA (75 micro g) treated rats whereas a higher dose did so only transiently. Pretreatment with GBR 12909 abolished these effects. These findings underline the neuropharmacological utility of the neonatal 6-OHDA treatment for studying brain receptor system adaptive changes underlying the respective functional alterations and as a possible laboratory model for clinical disorders.

Journal Article↗

PubMed2002

Predicting performance in ski and swim championships: effectiveness of mood, perceived exertion, and dispositional optimism.

Two studies were performed with young athletes to investigate the utility of three psychological tests regarding the prediction of sport performance: the Profile of Mood States. Ratings of Perceived Exertion, and Dispositional Optimism. In Study 1, young male and female cross-country skiers and ski-marksmen in final preparation for the Junior National Swedish Championships were tested. Measured 5 wk. before both competitions, the higher the optimism (LOT), the better performance. In Study 2, which tested young swimmers in preparation for the Senior National Swedish Championships, competitors who had the highest scores on optimism performed less well during the competitions. The results are interpreted to indicate that optimism presents an important factor for predicting achievement in sports.

Adult↗

PubMedDate not supplied

Neurodevelopmental liabilities in schizophrenia and affective disorders.

There is now considerable evidence that both schizophrenia and affective disorders have their origin at least in part in events that occur during early pre- and post-natal development. In the case of schizophrenia, many observations, for example, increased risk for schizophrenia in the offspring of mothers who had influenza A during their second trimester of pregnancy and evidence for abnormal neuronal migration in the cerebral cortex of post mortem tissue from schizophrenic patients, suggest that a second trimester insult may have occurred and that this insult may have increased the risk for the development of schizophrenia in late adolescence or early adulthood. Animal studies have found that rats that undergo exocitotoxic damage to the ventral hippocampus on postnatal day 7 develop exaggerated sensitivity to dopamine-stimulating drugs or to stressful stimuli that becomes apparent after sexual maturity but not before, providing a neurodevelopmental model of schizophrenia. Similarly, post-weaning social isolation leads to enhanced responses to dopaminergic drugs and to stress that emerges after sexual maturity. These animal models are proving to be valuable tools to study the neurobiological mechanisms mediating the influence of early insults to the nervous system on later behavioural functions. In the case of affective disorders, although the evidence is not as strong, a number of the same observations have been made suggesting that an insult during early ontogeny may lead to the development of affective disorders later in life. For example, retrospective studies of people with affective disorders showed that they were more likely to have attained motor milestones at a later age and to have had poorer academic performance as children. There is a wealth of evidence suggesting hyperfunctioning of the hypothalamic-pituitary-adrenal (HPA) axis in affective disorders. Animal studies have shown that early maternal deprivation can lead to lasting changes in the reactivity of the HPA axis to stressful stimuli, providing another link from early experience to adult psychopathology. Continued studies of the effects of pre- and early post-natal events on the development of the nervous system and the relationships of these events to schizophrenia or affective disorder will provide new insights into the mechanisms underlying these common neuropsychiatric illnesses.

Journal Article↗