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T Schallert

Publications and source records attributed to T Schallert.

At least 55 records · Page 3Linked to original sources
PubMed1993

Effects of in vitro ethanol and fetal ethanol exposure on glutathione stimulation of N-methyl-D-aspartate receptor function.

The present studies investigated the effects of glutathione (GSH; gamma-glutamylcysteinylglycine) and its oxidized form (GSSG) on neuronal N-methyl-D-aspartate (NMDA) receptor activation in both acute and chronic preparations of ethanol exposure. It was demonstrated using fura-2-loaded dissociated brain cells from newborn rat pups that both GSH and GSSG (0-4 mM) produced concentration-dependent increases in intracellular calcium similar to those produced by NMDA and other agonists of the NMDA receptor. GSH-stimulated calcium entry was not inhibited by low intoxicating concentrations of ethanol, which contrasts with ethanol's typical inhibitory effect on NMDA-stimulated receptor activation. Behavioral studies in adult rats demonstrated that ethanol-induced sleep times were significantly decreased when 10 microliters of GSSG (20 mM) were administered intracerebroventricularly approximately 5 min before an intraperitoneal injection of 20% (w/v) ethanol (3 g/kg). These findings suggest that the less potent effect of ethanol on GSH-stimulated calcium entry as well as the reduction in ethanol-induced sleep times may be related to the presence of glycine in the peptide. The glycine found in GSH may activate the glycine site and block or reduce ethanol's action on this site. It appears that although GSH may play an important role in the activation of the NMDA receptor, this action does not involve a process that is sensitive to acute ethanol exposure. In contrast, when rat pups were chronically exposed to ethanol via prenatal exposure before the fura-2 preparation, increases in NMDA- and GSH-stimulated calcium entry were significantly decreased relative to those in pair-fed and ad libitum-fed controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Subcortical deterioration after cortical damage: effects of diazepam and relation to recovery of function.

Agents which enhance the activity of gamma-aminobutyric acid (GABA) can severely disrupt behavioral recovery in rats following damage to the neocortex if delivered during a sensitive postoperative period. The mechanisms of this disruption have not been found. It has been suggested previously that the ipsilateral striatum and related structures may be transiently disabled after cortical lesions and that diazepam may interfere with restoration of function in these areas. In the present experiment, the subcortical anatomical effects of chronic (3 weeks) administration of diazepam, an indirect GABAergic agonist, were assessed following unilateral lesions of the anteromedial cortex (AMC) or the sensorimotor cortex (SMC) in rats. Atrophic and degenerative changes were examined in the striatum, substantia nigra and thalamus. Following either AMC or SMC lesions, there was a reduction in the size of the ipsilateral striatum and thalamus and a loss of neurons in the ipsilateral substantia nigra pars reticulata (SNr). After AMC lesions, striatal atrophy and neuron loss in the SNr were increased by the diazepam regimen relative to vehicle-treated controls. In addition, diazepam interfered with the behavioral recovery from somatic-sensorimotor asymmetries in AMC-lesioned rats. After SMC lesions, the sites of striatal and thalamic atrophy were different from that observed after AMC lesions, and the extent of atrophy and neuron loss was not exaggerated by diazepam treatment. Consistent with these data, diazepam did not significantly affect recovery from SMC lesions. These findings suggest that the long-term disruptive effects of diazepam on recovery of function after AMC lesions may be related to an augmentation of lesion-induced degeneration.

Animals↗
PubMed1992

Overgrowth and pruning of dendrites in adult rats recovering from neocortical damage.

Unilateral lesions to the forelimb representation (FL) area of the rat sensorimotor cortex caused a time-dependent increase in the dendritic arborization of layer V pyramidal neurons in the contralateral homotopic cortex. The increase in arborization was maximum at 2-3 weeks after the lesion, following which there was a partial reduction in dendritic branching. These neural morphological changes may be related to post-lesion behavioral changes in the use of the forelimbs.

Analysis of Variance↗
PubMed1992

Tolerance to the effects of ethanol on the speed and success of reaction time responding in the rat: effects of age and intoxicated practice.

An animal model of human reaction time (RT) was used to investigate the effects of age and intoxicated practice on the development of tolerance to the motor impairing effects of ethanol (EtOH). Young (8-9 month) and old (24-26 month) Fischer 344 rats were trained to release a lever in response to an auditory and visual stimulus in order to avoid mild footshock. The animals were divided into groups to receive either intoxicated (EtOH-before) or unintoxicated (EtOH-after) RT testing. Successful avoidance and response latencies were impaired in young and old rats after the initial exposure to EtOH (EtOH-before group). Tolerance developed to EtOH's effects on successful avoidance and on response latencies whether or not the rats received intoxicated RT practice; however, intoxicated practice facilitated tolerance development to EtOH's effects on successful avoidance but not on response latencies. While the initial sensitivity and the level of tolerance that developed to EtOH's effects were similar in young and old rats, the old rats were generally more sensitive to EtOH and developed tolerance at a slower rate. These results suggest that tolerance develops to the effects of EtOH on RT and that intoxicated practice can have different effects on the parameters of the behavioral response.

Aging↗
PubMed1992

MRI, brain iron and experimental Parkinson's disease.

Abnormal levels of brain iron have been reported in parkinsonism, which is characterized principally by degeneration of dopaminergic (DA) nigrostriatal neurons. There are conflicting reports, however, of both increased and decreased iron in parkinsonism. An animal model of parkinsonism was used to clarify the contribution of the loss of nigrostriatal DAergic neurons to abnormal iron accumulations. In rats with 6-hydroxydopamine induced unilateral DA depletion, brain iron deposition and its day-to-day stability was studied in vivo using T2-weighted magnetic resonance imaging (MRI) scans taken on 4 consecutive days beginning 1-2 months post-surgery and post-mortem by Perls'-DAB histochemical stain. Unilateral DA depletion (parkinsonism model) produced large day-to-day fluctuations in T2 relaxation time in the striatum. The T2 relaxation time in Sham control rats was relatively minor. The uptake and transport of iron by intrinsic cells of the striatum may vary, and this variability may have been exaggerated by the destruction of DAergic nigrostriatal neurons, which are known to modulate the activity of the intrinsic cells. Inconsistent reports of increased or decreased iron in parkinsonism may reflect, in part, single time-point measures of widely fluctuating iron.

Animals↗
PubMed1990

Functional subdivisions of the rat somatic sensorimotor cortex.

The behavioural impairments and subsequent recovery were studied in rats with circumscribed unilateral lesions in the somatic sensorimotor cortex (SMC). Lesions were made in the caudal forelimb region (CFL), the rostral forelimb region (RFL), the anteromedial cortex (AMC) or the hindlimb area. Rats with damage in the CFL produced a deficit in placing the forelimb contralateral to the lesion during exploratory locomotion on a grid surface. Rats with AMC damage circled in the direction ipsilateral to the lesion. Lesions in the CFL or AMC produced an ipsilateral somatosensorimotor asymmetry on the bilateral-stimulation test (responding to adhesive patches placed on the contralateral forelimb was slower) that recovered in 7 days following AMC lesions or 28 days following CFL lesions. Finally, RFL lesions produced an ipsilateral asymmetry on the bilateral-stimulation task that was more severe and enduring (recovery in 60 days). After behavioral recovery, the effects of an additional lesion placed in the homotopic contralateral cortex were examined (two-stage bilateral lesion). Rats receiving two-stage bilateral lesions in the RFL or CFL responded slower to tactile stimulation of the forelimb contralateral to the second lesion. In the case of CFL-damaged rats, placing deficits also appeared contralateral to the most recent injury. In contrast, rats receiving two-stage bilateral AMC lesions did not exhibit behavioral asymmetries following the second lesion. These results provide evidence to suggest that subdivisions of the rat SMC can be distinguished with lesion/behavioral experiments. Moreover, a comparison of the effects of unilateral and two-stage bilateral lesions may help in the parcellation of the rat SMC into functionally distinct subareas and provide a basis for studying the processes of recovery and maintenance of function following brain damage.

Animals↗
PubMed1990

Rescuing neurons from trans-synaptic degeneration after brain damage: helpful, harmful, or neutral in recovery of function?

Certain instances of neuronal degeneration secondary to brain damage might be functionally beneficial, and steps taken to protect against such degeneration may adversely affect behavioural outcome. After unilateral damage to the intrinsic neurons of the striatum, which includes GABAergic striatonigral projections, delayed trans-synaptic degeneration occurs in the ipsilateral substantia nigra pars reticulata (SNr). This degeneration was prevented by a 2-week regimen of muscimol delivered intraventricularly via osmotic minipumps. Muscimol is a direct-acting GABA agonist that presumably substituted for the absent GABA at the interface between the degenerating striatonigral GABAergic terminals and the GABAergic receptors located on SNr neurons. Sensorimotor asymmetry tests sensitive to unilateral striatal damage were carried out for 4 weeks to determine the functional consequences of the sparing of SNr neurons. Recovery of function was not improved. Instead, tactile extinction and hemiplegia were exaggerated in the contralateral forelimb. Other impairments were unaffected by the muscimol. The experiment was repeated using diazepam, rather than muscimol, to address the possibility that the disruptive effects of muscimol might reflect a more general disruptive influence on recovery processes. Diazepam, which has been shown in our lab to disrupt recovery of function after cortical lesions and to potentiate lesion-associated atrophy in remote subcortical structures, is an indirect-acting GABAergic agonist that requires GABA for its mechanism of action. Because GABAergic terminals at the SNr were destroyed, diazepam (as expected) failed to prevent SNr degeneration. Although diazepam presumably enhanced GABAergic synaptic activity in other brain regions, diazepam had no significant effect on postoperative behavioural function. Apparently, in the first experiment, the prevention of SNr degeneration per se was instrumental in the detrimental effects of muscimol. The rescued SNr neurons may have contributed to dysfunction because they lacked inhibitory GABAergic control. Transsynaptic degeneration secondary to brain damage was discussed as it might relate to release phenomena and their treatment by surgery or transmitter blocking agents in the clinical literature.

Animals↗
PubMed1990

Multilevel transneuronal degeneration after brain damage. Behavioral events and effects of anticonvulsant gamma-aminobutyric acid-related drugs.

Recent morphologic and behavioral studies of the effects of gamma-aminobutyric acid agents on transsynaptic degeneration after cortical and striatal damage are reviewed and discussed. Following unilateral lesions of the anteromedial cortex, mild atrophy appears in the ipsilateral striatum and substantia nigra pars reticulata. Long-term diazepam administration greatly enhances this degeneration, extends the degeneration into the thalamus, and severely disrupts recovery from somatosensory asymmetries. Following unilateral excitotoxic lesions of the striatum, progressive degeneration of neurons occurs in the substantia nigra pars reticulata and efferent targets in the thalamus. This degeneration can be prevented by chronic infusion of muscimol, a gamma-aminobutyric acid agonist. Unexpectedly, this treatment did not facilitate recovery from somatosensory asymmetries. Recovery in muscimol-treated animals was impaired relative to saline-treated controls. Thus, gamma-aminobutyric acid agonists either may enhance or prevent neural atrophy secondary to brain damage, but the behavioral outcome appears to depend importantly on the excitatory and inhibitory characteristics of the affected networks.

Animals↗
PubMed1990

Effects of MK-801 on recovery from sensorimotor cortex lesions.

Histologic evidence suggests that drugs acting as noncompetitive antagonists at the N-methyl-D-aspartate receptor can have beneficial or pathologic effects on central nervous system neurons. In the present experiments we examined the effects of MK-801 on recovery of behavioral function after unilateral lesions in the rat somatic sensorimotor cortex. In the first experiment, rats with unilateral sensorimotor cortex lesions were given either MK-801 (1 mg/kg) or saline 12-16 hours after surgery. Additional injections were given on postoperative days 2, 4, and 6. Behavioral tests measured somatosensory asymmetries (i.e., bilateral tactile stimulation tests) and forelimb placing. After creation of sensorimotor cortex lesions, rats showed an ipsilateral somatosensory bias and an impairment in placing the contralateral forelimb. Rats treated with MK-801 recovered slightly faster than saline-treated animals as measured by a bilateral tactile stimulation test (p less than 0.05). In contrast, there was no significant difference between the groups in the recovery of forelimb placing. In a second experiment, rats with sensorimotor cortex lesions were treated with a single injection of MK-801 after behavioral recovery. Twenty hours after the MK-801 injection, rats with sensorimotor cortex lesions showed a reinstatement of the placing deficits. The impairment endured for at least 7 days after injection. These behavioral data support the idea that MK-801 can have either beneficial or detrimental effects when administered after brain damage.

Animals↗
PubMed1989

Co-administration of Ro 15-1788 prevents diazepam-induced retardation of recovery of function.

Following unilateral lesions of the anteromedial cortex, recovery from somatosensory asymmetry reliably occurs within about 10 days. Chronic exposure to diazepam significantly delays this recovery. In the present study, co-administration of Ro 15-1788, a benzodiazepine antagonist (i.e. it blocks the negative and positive allosteric modulation of GABA), prevented diazepam-induced retardation of recovery from somatosensory asymmetry. Nocturnal ambulatory (motor) activity was not different between rats receiving diazepam-alone and those receiving Ro 15-1788 in combination with diazepam. These data suggest that the benzodiazepine receptor is importantly involved in the detrimental effects of diazepam on recovery, and that non-specific behavior sedation plays little or no role.

Animals↗
PubMed1989

Effects of route of administration of ethanol on high-speed reaction time in young and old rats.

The blood ethanol concentrations (BECs) and reactive capacity of young (8 months) and old (24 months) male Fischer 344 rats were compared at 5, 10, 20, 45, 65, and 90 min following the administration of ethanol (EtOH). The time-dependent effects of intragastric intubation (IG; 3 g/kg) and intraperitoneal injection (IP; 1.5 g/kg) of EtOH (20% w/v) were determined. Subsequent to IG delivery, BECs rose most rapidly within the first 20 min, but did not reach peak levels until 90 min for both young (240 mg/dl) and old rats (250 mg/dl). Following IP injections, BECs escalated within 5 min to 250 mg/dl in the young, to 175 mg/dl in the old, and declined gradually to a stabilized value of 150 mg/dl (young) and 130 mg/dl (old). The old rats never achieved the high BECs seen in the young. Reactive capacity, a measure of auditory/visual reaction time, was inversely related to BECs. As BECs (IP) declined, performance improved at a similar rate in both age groups, although the old rats' performance was more impaired than that of the young. However, BEC per se was not an adequate predictor of reactive capacity. When EtOH was delivered by IG so that BECs remained high for long periods of time, reactive capacity was far less impaired compared with IP delivery in which comparable BECs were present for only a few minutes. The possibility was noted that behavioral tolerance may have developed during the 90-min post-EtOH period, and that the IP delivery method may disrupt behavior in ways independent of brain ethanol levels.

Aging↗
PubMed1988

'Disengage' sensorimotor deficit following apparent recovery from unilateral dopamine depletion.

Sensorimotor behavior in Long-Evans rats was evaluated acutely and chronically after unilateral dopamine depletion caused by infusions of 6-hydroxydopamine into the nigrostriatal system. In each rat, control infusions were delivered to the opposite hemisphere and a noradrenaline uptake blocker was used as a pretreatment to help protect noradrenaline cells. During the first few postoperative weeks, head movement reactions to repetitive tactile-perioral stimulation contralateral to the dopamine-depleted hemisphere were delayed but not eliminated. With recovery, facilitated by special training, the rats were able to respond quickly. However, two lasting abnormalities were observed. First, the types of head-orienting movements directed toward contralateral stimulation were different from that directed toward ipsilateral stimulation. Second, when the animals were engaged in eating behavior there was a complete failure to orient to contralateral stimulation, whereas they instantly disengaged from eating to orient to ipsilateral stimulation. When not eating, orienting was rapid and reliable to stimulation of either side of the body. These data may have implications for the role of the striatum and connected structures in the organization and integration of sensorimotor and ingestive behavior.

Animals↗
PubMed1988

Seizures and recovery from experimental brain damage.

The effects of the gamma-aminobutyric acid antagonist, pentylenetetrazol (PTZ), on recovery from somatosensory and motor asymmetries after unilateral sensorimotor cortex lesions were investigated. Behavior was assessed using a bilateral tactile stimulation test and a measure of forelimb motor coordination. Immediately after surgery, the PTZ-treated and saline (SAL) control groups both exhibited severe ipsilateral behavioral asymmetries. Rats receiving PTZ recovered significantly faster from somatosensory asymmetry than those receiving SAL. Recovery was complete in the PTZ group within 3 postoperative weeks, while the SAL group failed to reach a comparable level until 2 months after surgery. There was no difference between PTZ and SAL groups on recovery of forelimb motor coordination. No difference in lesion size between the SAL and the PTZ groups could be found. These data are consistent with the hypothesis that post-traumatic neuronal depression may contribute to the severity of sensorimotor deficits observed after brain damage.

Animals↗
PubMed1988

Striatal dopamine and the interface between orienting and ingestive functions.

Recent lesion experiments have implicated forebrain catecholaminergic projections in a unique switching mechanism that enables sensory orientation to occur during ongoing feeding behavior. Unit recording studies indicate that there is a population of neurons in the striatum that respond to tactile stimulation only while an animal is eating. These sensory-related cells may serve as part of a system that diverts attention away from ingestive behavior. In the present study, 6-hydroxydopamine was infused directly into the striatum in rats to eliminate the dopaminergic input specifically to this region. The animals were tested for their reactions to tactile stimulation of the vibrissae during or in the absence of eating. During noneating trials, orienting was rapid and reliable to stimuli presented on either side of the body midline. While eating, contralateral orienting never occurred, even when the stimulation was intense, whereas ipsilateral orienting was unaffected. It was suggested that the capacity to disengage from ingestive behavior may depend importantly on the integrity of dopaminergic input to the striatum.

Animals↗
PubMed1988

Aging and atropine effects on spatial navigation in the Morris water task.

A recent animal model that has been particularly useful in the neurobiology of aging has been the age-related decline of spatial information processing capacity in Sprague-Dawley rats measured in the place-learning water task developed by Morris (1981). In the first experiment of the present study, place behavior was examined in young (6 months), old (23-24 months), and very old (28 months) rats of another strain, Long-Evans. As an analogue of aging-related cholinergic dysfunction the effects of atropine sulfate (5-50 mg/kg), an anticholinergic drug that is known to disrupt behavior in this task, also was determined. Place navigation was not impaired in undrugged rats, even those in the oldest age group. Rats treated with atropine showed dose-dependent deficits. In a second experiment, young (4-5 months), old (18-20 months), and very old (28 months) Fischer-344 rats were examined. Place navigation was impaired in the old rats. The very old (28 months) rats could not swim well enough to be tested adequately. Although nonspatial deficits associated with aging may be found across most strains tested, there appear to be very large strain-related differences in spatial processing ability as a function of age.

Aging↗
PubMed1987

Somatosensorimotor function of the superior colliculus, somatosensory cortex, and lateral hypothalamus in the rat.

The role of the superior colliculus in multimodal sensory function is unsettled, in large part because a clear distinction between the somatosensory effects and the postural/motor effects of damage to the deep layers of the superior colliculus has not been obtained. Unilateral lesions of the entire superior colliculus impair orienting of the head and eyes to tactile, visual, and auditory stimuli presented on the side of the body contralateral to the lesion; however, even in the absence of sensory stimulation animals with such a lesion tend to circle ipsiversively and fail to make contralateral head movements. To determine whether or not unilateral damage to the superior colliculus produces a somatosensory asymmetry independently of head movement/circling biases, a neurological test was used in which lateral head or trunk movements were not required. Small pieces of adhesive-backed paper were attached to each forelimb and the latencies to contact and remove the stimuli were recorded. A battery of standard neurological tests was administered as well. The entire superior colliculus was removed unilaterally, and for comparison, the sensorimotor cortex or lateral hypothalamus were damaged in additional groups. Lesions of the superior colliculus produced the expected deficit in contralateral orienting and ipsilateral circling/postural biases, but failed to produce a somatosensory asymmetry in the head movement-independent sensorimotor test. In contrast, both sensorimotor cortex and lateral hypothalamus lesions produced a severe asymmetry in the head-movement-independent sensorimotor test. We conclude that the superior colliculus is involved in the control of lateral head movements and that its role in somatosensory function is fundamentally different from that of the sensorimotor cortex or lateral hypothalamus regions.

Animals↗