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W J Schmidt

Publications and source records attributed to W J Schmidt.

At least 109 records · Page 6Linked to original sources
PubMed1990

6-Hydroxydopamine lesion of the rat prefrontal cortex increases locomotor activity, impairs acquisition of delayed alternation tasks, but does not affect uninterrupted tasks in the radial maze.

The role of mesocortical dopamine neurons in locomotion and acquisition of various delayed and uninterrupted maze tasks was investigated in the rat. Dopaminergic terminals of the medial prefrontal cortex were lesioned by stereotaxically guided injections of the selective neurotoxin 6-hydroxydopamine (6-OHDA), while noradrenergic neurons were protected by systemically administered desipramine. 6-OHDA lesions resulted in a selective depletion of dopamine and its metabolite, dihydroxyphenylacetic acid, in the prefrontal cortex but not in subcortical structures. Prefrontal serotonin was not depleted. 6-OHDA-cloned rats performed uninterrupted alternation tasks (spontaneous and reinforced alternation) in the radial maze in the same manner as controls, whereas performance of delayed alternation in the T-maze and the radial maze was impaired in lesioned rats. In addition, locomotor activity during maze performance was increased in lesioned rats. Based on the hypothesis that increased motor activity and impaired delayed alternation performance are due to increased susceptibility to interfering stimuli, we propose tentatively that prefrontal dopamine may function to suppress interference during the delay period of certain cognitive tasks.

Afferent Pathways↗
PubMed1990

MK-801-induced stereotypy and its antagonism by neuroleptic drugs.

MK-801 [(+)-5-methyl-10,11-dihydroxy-5H-dibenzo-(a,d)cyclohepten-5,10-imi ne hydrogen maleate], which blocks glutamatergic transmission at the NMDA-receptor-gated ion channel, induced stereotypies which are similar to those found after intrastriatal injections of AP-5, e.g. sniffing and locomotion. Tests in familiar or unfamiliar environment (non-stressful or stressful situation) did not qualitatively change MK-801-induced effects. Haloperidol (0.1 mg/kg, IP) delayed the onset and shortened the duration of MK-801 (0.16; 0.33 mg/kg, IP)-induced stereotypy whereas clozapine (5 mg/kg, SC) potently antagonized it. However, exact quantification of sniffing, measured in an experimental chamber designed for this purpose, revealed an antagonism by both drugs, haloperidol as well as clozapine. Stereotypy is considered to represent an animal model of schizophrenia, and the antagonism of stereotypy with classical (haloperidol) as well as with atypical (clozapine) antipsychotic drugs is in accordance with the glutamate hypothesis of schizophrenia.

Animals↗
PubMed1989

Effects of intrastriatal blockade of glutamatergic transmission on the acquisition of T-maze and radial maze tasks.

Prefrontal cortex and neostriatum constituting the prefrontal system are connected by glutamatergic neurones. The involvement of this corticostriatal projection in control of maze performance of rats was investigated. Glutamatergic transmission mediated by N-methyl-D-aspartate (NMDA) receptors was blocked by intrastriatal injections of dl-2-amino-5-phosphonovaleric acid (AP-5) (50 nmole in 0.5 microliters). In experiment 1, intrastriatal AP-5 was found to increase the number of errors during acquisition of a delayed alternation task in a T-maze. In experiment 2, the effect of intrastriatal AP-5 on acquisition of different 8 arm maze tasks was investigated. AP-5 did not affect the number of reentries on spontaneous and reinforced alternation; pre- and postdelay errors on delayed alternation were not altered. Therefore, intrastriatal NMDA receptor blockade impairs acquisition of a delayed alternation in a T-maze, while intrastriatal blockade of NMDA receptors does not affect acquisition of different 8 arm maze tasks. The impairment in the T-maze task appears not to be due to deficient acquisition of spatial information per se, since 8 arm maze performance is intact. Instead, repeated delays in the T-maze task seem to be the critical component that gives difficulties in acquisition. These difficulties in bridging successive temporal discontiguities were attributed to an increased susceptibility to external and internal interfering stimuli during delays. Thus, striatal NMDA receptors within the prefrontal system may be involved in correct response retention over the duration of delays.

2-Amino-5-phosphonovalerate↗
PubMed1989

Anticataleptic effects of the N-methyl-D-aspartate antagonist MK-801 in rats.

The N-methyl-D-aspartate (NMDA) antagonist MK-801 was administered to rats in three doses (0.08, 0.16, 0.33 mg/kg) in order to examine its effects on catalepsy that was induced by haloperidol (0.5 mg/kg). The degree of catalepsy was assessed 30 and 60 min after application of drugs by placing the rat on a horizontal bar, on a podium and on a vertical grid. Animals having received saline and haloperidol showed a higher degree of catalepsy than animals having received MK-801 and haloperidol (except for the lowest dose of MK-801). These findings may suggest a therapeutic potential of MK-801 and possibly of other NMDA antagonists in the treatment of Parkinson's disease.

Animals↗
PubMed1988

Haloperidol- and apomorphine-induced changes in pup searching behaviour of house mice.

Maternal pup searching behaviour of lactating house mice treated with apomorphine, haloperidol or saline was examined on a running board with a central depression as a nest. Pup searching was elicited by artificial ultrasonic stimuli: a female moved out from the nest either towards a 50 kHz tone (key stimulus) which is adequate to activate species specific pup searching behaviour or towards a 20 kHz tone (neutral stimulus), thus showing her preference for one of these stimuli. Under apomorphine (0.00625; 0.0125; 0.025 mg/kg) the females preferred the key stimulus. Nevertheless apomorphine (0.00625-0.025 mg/kg) prolonged response latencies and shortened the duration of pup searching. At the highest dose (0.05 mg/kg), apomorphine induced stereotyped sniffing. Haloperidol (0.025; 0.05; 0.1 mg/kg) had opposite effects to apomorphine: it lowered the threshold for elicitation, shortened response latencies and prolonged the duration of pup searching. Females treated with haloperidol (0.025-0.1 mg/kg) did not prefer the key stimulus. Changes in response elicitation and in the performance of pup searching induced by apomorphine and haloperidol, respectively, were assumed to be due to i) a reduced and an increased responsiveness to external stimuli respectively, ii) an enhanced and a reduced tendency for response switching respectively, and iii) a preference for spontaneous behaviour in apomorphine-treated females, with an increased dependence on exteroceptive stimuli following haloperidol.

Acoustic Stimulation↗
PubMed1988

Behavioural effects of N-methyl-D-aspartate in the anterodorsal striatum of the rat.

N-methyl-D-aspartate (NMDA) (0.5 and 1 microgram/0.5 microliter) bilaterally injected into the anterodorsal striatum of rats reduced locomotion, sniffing, rearing and feeding upon presentation of palatable food. Consequently, the number of all behavioural bouts exhibited was reduced and the duration of akinetic phases was prolonged. These results are discussed in connection with previous findings showing that the NMDA receptor blocker DL-2-amino-5-phosphonovaleric acid (AP-5) injected at the same site - produced opposite effects: AP-5 enhanced locomotion, rearing, sniffing as well as the total number of behavioural bouts exhibited.

Animals↗
PubMed1987

Antagonism of AP-5- and amphetamine-induced behaviour by timelotem as compared with clozapine and haloperidol.

Bilateral intrastriatal injection of DL-2-amino-5-phosphonovaleric acid (AP-5), that blocks glutamatergic transmission at the N-methyl-d-aspartate preferring receptor, induces sniffing and body turns and reduces grooming in rats. Timelotem, a representative of the newly developed chemical class of anellated benzodiazepines antagonized specifically AP-5-induced sniffing and body turns. Classical (haloperidol) as well as atypical (clozapine) neuroleptics had recently been shown to antagonize AP-5-induced sniffing; clozapine, like timelotem, but not haloperidol, additionally antagonized AP-5-induced body turns. Further, timelotem antagonized amphetamine-induced stereotyped behaviour in rats, but was found less active than haloperidol in this test. Comparing the activity of drugs in both paradigms revealed that haloperidol inhibited AP-5-induced sniffing and amphetamine-induced stereotypies within the same dose range, but timelotem and clozapine were found more potent in the AP-5 test than in the amphetamine test. Thus, detailed drug profiles discriminate timelotem and clozapine from haloperidol, linking timelotem again to atypical antipsychotic compounds.

2-Amino-5-phosphonovalerate↗
PubMed1986

Oestrogen modulates dopamine-controlled behaviours in the male ferret.

Oestradiol (100 micrograms/kg) was administered to male ferrets on three successive days. Two and three days after the last oestradiol injection the effects of apomorphine (0.5 mg/kg) on stereotyped, predatory and scent marking behaviour were intensified. Thus, three days of oestradiol administration produced a supersensitive dopaminergic system two days after the last oestradiol injection. However, no initial antidopaminergic effect of oestradiol could be demonstrated one day after the last oestradiol injection.

Animals↗
PubMed1986

Intrastriatal injection of DL-2-amino-5-phosphonovaleric acid (AP-5) induces sniffing stereotypy that is antagonized by haloperidol and clozapine.

DL-2-amino-5-phosphonovaleric acid (AP-5), which blocks glutamatergic transmission at the NMDA-preferring receptor, was injected into the antero-dorsal striatum of rats. AP-5-induced behavioural changes were assessed i) using a stereotypy rating scale and ii) using an experimental chamber designed to quantify sniffing. In both behavioural situations it was shown that AP-5 (10 micrograms/0.5 microliter) induced continuous intensive sniffing similar to that induced by small doses of systemically administered amphetamine or apomorphine. However, oral stereotypies were not induced by AP-5. Systemically injected clozapine (5 and 10 mg/kg SC) as well as haloperidol (0.1 mg/kg IP) antagonized AP-5-induced sniffing. These results show that besides dopamine receptors, NMDA receptors are involved in the control of sniffing. In behavioural terms, the effect of glutamate mediated by the NMDA receptor in the striatum is opposite to that of dopamine.

2-Amino-5-phosphonovalerate↗
PubMed1986

Annual rhythm and hormonal control of predatory behavior in female ferrets.

The predatory behavior of female ferrets shows seasonal fluctuations which appear to be affected by estradiol. Under natural lighting conditions in the laboratory the annual rhythm of the behavior was observed during anestrus, estrus, pregnancy, pseudopregnancy and lactating period. Females in heat failed to show predatory behavior whereas females in anestrus killed their prey. Exposure of anestrous ferrets to a prolonged illumination (LD 16:8) during winter induced an estrus which inhibited predatory behavior. When estrus was terminated with human chorionic gonadotropin (HCG), predatory behavior did not further regress as it did in control runs. Thus, during the period of estrus, when estrogen levels are presumably high, predatory behavior was inhibited. To prove a possible interdependency of estrogen and predatory behavior, estradiol-17 beta-valerat was chronically administered. This treatment induced the estrous cycle one day after the first injection. Inhibition of predatory behavior occurred following a delay of 28 days. Thus, fluctuations of estradiol levels are a factor which may affect fluctuations of predatory behavior in female ferrets.

Animals↗
PubMed1984

L-dopa and apomorphine disrupt long- but not short-behavioural chains.

Apomorphine (0.01-0.5 mg/kg) disrupted fighting between two male ferrets. The number of bites and neck nuzzling were decreased dose-dependently. At 0.05 and 0.1 mg/kg scent-marking and collateral behaviour were increased, at 0.5 mg/kg stereotyped sniffing was induced. L-dopa (120 mg/kg + 30 mg/kg benserazide) exerted similar effects to apomorphine 0.05 mg/kg. Thus, the dopamine (DA) agonists increased short chain responses but disrupted long ones. Haloperidol (0.2 mg/kg) facilitated inter-male fighting. The number of bites increased, but scent-marking and collateral behaviour were selectively suppressed. Thus, the persistency of the long behavioural chain was enhanced. Since, at lower doses, DA-agonists expand and DA-antagonists selectively narrow the range of exhibited behavioural responses, it is suggested that the degree of stimulation of central DA-receptors determines the animal's ability to suppress responses that compete with ongoing behaviour.

Agonistic Behavior↗
PubMed1983

Involvement of dopaminergic neurotransmission in the control of goal-directed movements.

Changes produced in dopamine (DA) activity, by administration of the DA-antagonists metoclopramide (10 mg/kg IM) and tiapride (16 mg/kg IM) and of the DA agonists apomorphine (0.5 and 1 mg/kg IM) and bromocriptine (8 mg/kg orally), specifically modified predatory behavior in the ferret. Sulpiride (40 mg/kg IP and 90 mg/kg IM) did not change the behavior. The number of bites necessary to kill the prey was reduced by metoclopramide and tiapride. The number of bites after the death of the prey was not changed. The latency from the first bite to the death of the prey was shortened. Apomorphine and bromocriptine increased the number of bites. The DA receptor blockers haloperidol, chlorpromazine, and clozapine had similar effects to metoclopramide and tiapride, and the DA agonist L-dopa had similar effects to apomorphine and bromocriptine. The pattern of results indicated that, considering the two major DA receptor types, D-2 receptors or D-2 in combination with D-1 but not D-1 receptors alone were involved in the control of goal-directed movements. The results also provided some evidence that blockade of these DA receptors caused a narrowing of the range of exhibited behavioral responses. Stimulation of the DA receptors had opposite effects.

Animals↗