Biomedical subjects

W J Schmidt

Publications and source records attributed to W J Schmidt.

At least 55 records · Page 3Linked to original sources

PubMed1999

Functional heterogeneity of the rat medial prefrontal cortex: effects of discrete subarea-specific lesions on drug-induced conditioned place preference and behavioural sensitization.

While the principal components of the brain reward system, the nucleus accumbens septi and the ventral tegmental area have received much attention, their efferent and afferent structures have not been investigated to the same degree. One major input to this system originates from the medial prefrontal cortex (mPFC) which is not a homogenous structure but can be divided into different subareas that can be distinguished on anatomical and possibly functional grounds. We examined the effects of discrete bilateral quinolinic acid lesions (45 nmol/0.5 micro(L)) of each of the mPFC subareas, the infralimbic (il), prelimbic (pl) and the anterior cingulate (cg) mPFC, on the conditioned place preference (CPP) and psychomotor activation induced by several drugs. Lesions of the il mPFC blocked CPP induced by morphine (10 mg/kg) and CGP37849 [DL-(E)-2-amino-4-methyl-5-phosphono-3-pentic acid, a competitive N-methyl-D-aspartate receptor antagonist; 10 mg/kg]. Lesions of the pl mPFC blocked CPP induced by cocaine (15 mg/kg) and CGP37849, and lesions of the cg mPFC only blocked CGP37849-induced CPP. Lesions of the whole mPFC blocked morphine-, cocaine- and CGP37849-induced CPP. None of the lesions affected DL-amphetamine (4 mg/kg)-induced CPP. During the conditioning period, none of the lesions affected amphetamine-induced psychomotor activation and sensitization, whereas both phenomena were attenuated by pl and whole mPFC lesions in the case of cocaine, and by il and whole mPFC lesions in the case of morphine. These results show that the different mPFC subregions have distinct functional roles in the generation of behavioural effects produced by different classes of drugs. This heterogeneity should be taken into account in future studies addressing the role of the mPFC in drug reward and sensitization.

2-Amino-5-phosphonovalerate↗

PubMed1998

The mGluRs group II agonist (2S,3S,4S)-alpha-carboxycyclopropyl-glycine induces catalepsy in the rat, which is pronouncedly antagonised by dizocilpine and D,L-amphetamine.

Glutamate in the basal ganglia has important roles in the regulation of motor processes and this is the first study on the role of inhibitory, group II, metabotropic glutamate receptors (mGluRs) for motor behaviour. The group II agonist (2S,3S,4S)-alpha-carboxycyclopropyl-glycine (L-CCG I) dose dependently induced catalepsy, infused intracerebroventricular (i.c.v.) in rats. The catalepsy was antagonised by dizocilpine and D,L-amphetamine, i.e. by N-methyl-D-aspartate receptor blockade and dopamine receptor activation, respectively. Psychotomimetic side effects limit the clinical use of previously suggested postsynaptic approaches to reduce pathological glutamatergic overactivation, as occuring in epilepsy, ischemia or trauma, but group II agonists provide a new presynaptic approach. Since the catalepsy-induction predicts a lack of psychotomimetic side effects, this study indicates that presynaptic approaches on mGluRs may be more suitable in these situations.

Amino Acids, Dicarboxylic↗

PubMed1998

The anti-craving drug acamprosate inhibits the conditioned place aversion induced by naloxone-precipitated morphine withdrawal in rats.

The anti-craving drug acamprosate (Ca N-acetylhomotaurinate) is therapeutically used to prevent a relapse in weaned alcoholics. In the present place conditioning study, the effect of this compound on the motivational impact of morphine withdrawal was examined. Withdrawal was precipitated in rats by administration of the opioid antagonist naloxone (0.1 mg/kg, s.c.) 5-6 days after the subcutaneous implantation of a 75 mg morphine pellet. Aversion against the naloxone-paired cues was observed after conditioning in the drug-free state. The acquisition of conditioned place aversion was completely inhibited by the pretreatment with acamprosate (200 mg/kg, i.p.) 12 h and 30 min prior to conditioning. These results clarify that acamprosate inhibits the motivational component of morphine withdrawal and suggest that ethanol and opiates share similar properties in the neuronal mechanisms of conditioned withdrawal and craving.

Acamprosate↗

PubMed1998

The development of cocaine-induced behavioral sensitization is affected by discrete quinolinic acid lesions of the prelimbic medial prefrontal cortex.

The brain circuitry thought to be involved in the development of behavioral sensitization to psychostimulants consists of the mesocorticolimbic dopaminergic system and its afferent and efferent structures, including the medial prefrontal cortex (mPFC). The mPFC can be further subdivided into several regions, one of which being the prelimbic area (PL). This study sought to examine the role that the PL mPFC plays in the development of cocaine-induced behavioral sensitization. Intact and lesioned animals were treated with cocaine (10 mg/kg) or saline once daily for 14 days and tested in an open field and in a 'sniffing box' on day 1, and then again on day 16, 48 h after the last drug injection. Behavioral parameters analyzed included locomotion, rearing, sniffing and grooming. It was found that the lesion affected the development of sensitization to cocaine. In the open field, lesioned animals showed a smaller increase in locomotion and rearing, but a larger increase in grooming as compared to the intact animals. While total sniffing scores in the sniffing box remained unchanged with repeated cocaine in the non-lesioned group, the lesioned group showed a decrease in sniffing. Finally, similar to what was seen in the open field, lesioned rats showed a strong tendency towards increased grooming. These results show that small discrete lesions of the PL mPFC can affect the development of behavioral sensitization to cocaine in a characteristic way. It is suggested that this effect might be mediated by the destruction of descending glutamatergic projections from the mPFC to the ventral tegmental area and/or nucleus accumbens.

Animals↗

PubMed1998

Blockade of morphine- and amphetamine-induced conditioned place preference in the rat by riluzole.

Previous studies have shown that antagonists at glutamatergic N-methyl-D-aspartate (NMDA) or alpha-amino-3-hydroxy-5-methyl-4-isoxazolpropionic acid (AMPA) receptors can disrupt the development or expression, respectively, of conditioned place preference (CPP) induced by drugs of abuse. The present study examined the effects of inhibition of presynaptic glutamate release by riluzole on the development of morphine- and amphetamine-induced CPP. Morphine (10 mg/kg), D,L-amphetamine (4 mg/kg) and riluzole (4 mg/kg) itself each produced a significant CPP; however, when riluzole was co-administered with morphine or amphetamine during the conditioning sessions, no CPP developed. It is concluded that non-specific disruption of glutamatergic neurotransmission prevents the development of morphine- and amphetamine-induced CPP.

Amphetamine↗

PubMed1998

Dopamine-glutamate interactions in the basal ganglia.

In an attempt to formulate a working hypothesis of basal-ganglia functions, arguments are considered suggesting that the basal ganglia are involved in a process of response selection i.e. in the facilitation of "wanted" and in the suppression of "unwanted" behaviour. The meso-accumbal dopamine-system is considered to mediate natural and drug-induced reward and sensitization. The meso-striatal dopamine-system seems to fulfill similar functions: It may mediate reinforcement which strengthens a given behaviour when elicited subsequently, but which is not experienced as reward or hedonia. Glutamate as the transmitter of the corticofugal projections to the basal ganglia nuclei and of the subthalamic neurons is critically involved in basal ganglia functions and dysfunctions; for example Parkinson's disease can be considered to be a secondary hyperglutamatergic disease. Additionally, glutamate is an essential factor in the plasticity response of the basal-ganglia. However, opposite to previous suggestions, the NMDA-receptor blocker MK-801 does not prevent psychostimulant- nor morphine-induced day to day increase (sensitization) of locomotion. Also the day to day increase of haloperidol-induced catalepsy was not prevented by MK-801.

Basal Ganglia↗

PubMed1998

The role of NMDA receptors in the slow neuronal degeneration of Parkinson's disease.

Parkinson's disease is a disorder, in which neurons of various neuronal systems degenerate. Furthermore, in such degenerating neurons, the cytoskeleton seems to be affected. In this respect, Parkinson's disease resembles Alzheimer's disease. Since it has been shown, that elevated levels of intracellular calcium can disrupt the cytoskeleton and that the stimulation of glutamate (NMDA) receptors can cause high intracellular concentrations of calcium, it has been suggested, that the stimulation of glutamate receptors plays a role in the slow degeneration in Alzheimer's and Parkinson's disease. In case of the degeneration of the dopaminergic nigrostriatal system in Parkinson's disease, neurons that contain calcium binding protein appear to be less vulnerable than the neurons that lack it, suggesting that calcium binding protein might protect these neurons from degeneration by preventing that cytosolic calcium concentrations increase excessively. And, since there is in the nigrostriatal system a glutamatergic afferent pathway (the prefrontonigral projection) and since dopaminergic nigrostriatal neurons contain postsynaptic NMDA receptors, glutamatergic excitation may play a role in the degeneration of the nigrostriatal system in Parkinson's disease. If so, it may be possible to protect the neurodegeneration of these dopaminergic neurons by NMDA receptor antagonists.

Alzheimer Disease↗

PubMed1998

Riluzole, a glutamate release inhibitor, and motor behavior.

Riluzole (2-amino-6-trigluoromethoxy benzothiazole) has neuroprotective, anticonvulsant, anxiolytic and anesthetic qualities. These effects are mediated by blockade of glutamate transmission, stabilizing of sodium channels and blockade of gamma-aminobutyric acid (GABA) reuptake. The action profile of riluzole is dominated by its effects on glutamate transmission which are predominately mediated by N-methyl-D-aspartate (NMDA) receptor-linked processes in vitro. In vivo studies show that blockade and stimulation of the different NMDA receptor complex binding sites or AMPA receptors modulate motor behavior in a characteristic manner. It was therefore interesting to examine if blockade of glutamatergic transmission by riluzole induced similar behavioral effects as direct NMDA/AMPA receptor antagonists and if these effects are mediated by a specific receptor. The effects of riluzole alone and in combination with several other neuroactive compounds on the central nervous system was assessed by behavioral paradigms to evaluate sniffing behavior, locomotion, ataxia and rigidity. Accompanying compounds included the NMDA receptor agonist NMDA, the partial glycine site agonist D-cycloserine (DCS), and the alpha-amino-3-hydroxy-5-phenyl-4-isoxazolepropionic acid (AMPA) receptor antagonist GYKI 52466 [1-(4-aminophenyl)-4-methyl-7,8-methylenedioxy-5H-2,3-benzo-diazepine HCl]. Riluzole influenced neither stereotyped sniffing behavior nor locomotion but impaired motor coordination and attenuated rigidity induced by blockade of dopamine D1 and D2 receptor antagonists when given alone. At higher doses spontaneous behavioral activity decreased and motor coordination was more impaired. Augmentation of the riluzole effects were observed when NMDA, but not GYKI 52466, was coadministered. The glycine site agonist DCS increased the anticataleptic properties of riluzole. The results indicate that when given alone, riluzole has a behavioral profile resembling that of competitive NMDA receptor antagonists. However, coadministration of riluzole with NMDA/AMPA receptor ligands suggests that this assumption is incorrect, and that riluzole affects glutamatergic transmission by a more indirect mechanism. Nevertheless, the profile of riluzole together with its pre- and postsynaptic blockade of glutamatergic transmission implies beneficial properties in diseases where an overactive glutamate system induces chronic neurotoxicity and/or acute behavioral effects.

Animals↗

PubMed1998

Does the noncompetitive NMDA receptor antagonist dizocilpine (MK801) really block behavioural sensitization associated with repeated drug administration? .

The term 'behavioural sensitization' refers to the progressively augmented behavioural response that is produced by many drugs of abuse upon their repeated administration. From most of the available data, it has been concluded that co-administration of an N-methyl-D-aspartate (NMDA) receptor antagonist [such as dizocilpine (MK801)] together with the sensitizing drug can block the development of behavioural sensitization. However, the picture might not be that simple. Recent experimental evidence suggests that instead of blocking sensitization, co-administration of dizocilpine enhances the effect of the the sensitizing drug or has more complex effects on the development of sensitization. In this article, Thomas Tzschentke and Werner Schmidt present these two different views and emphasize that the conclusions that can be drawn from sensitization experiments about the effects of dizocilpine and related drugs on behavioural plasticity crucially depend on how, when and under what conditions a test for sensitization is conducted.

Animals↗

PubMed1998

Discrete quinolinic acid lesions of the rat prelimbic medial prefrontal cortex affect cocaine- and MK-801-, but not morphine- and amphetamine-induced reward and psychomotor activation as measured with the place preference conditioning paradigm.

As a part of the mesocorticolimbic system, the medial prefrontal cortex (mPFC) is thought to participate in the regulation of locomotor activity, motivation and reward. The mPFC consists of at least three different subareas. In previous lesion studies examining this region usually large parts of the mPFC were destroyed, with little discrimination between the different subareas. Therefore, this study was designed to selectively lesion the prelimbic area of the mPFC using a relatively low dose of quinolinic acid. In a conditioned place preference (CPP) experiment, lesioned and control animals were treated with cocaine (15 mg/kg), amphetamine (4 mg/kg), morphine (10 mg/kg) or MK-801 (0.3 mg/kg) to induce CPP. The lesion blocked the development of CPP only in animals receiving cocaine, but not in animals receiving amphetamine or morphine. MK-801 failed to produce a CPP in both lesioned and unlesioned animals. During the conditioning experiment, the acute locomotor response to the different drugs was also measured. Only the response (in terms of locomotion and rearing) to cocaine and MK-801 was reduced to a significant extent by the lesion, while the response to amphetamine and morphine was not affected. Also, the lesions did not cause any changes in the spontaneous activity of the animals when tested without drug. These results show that even small lesions of the prelimbic subarea of the mPFC are sufficient to produce behavioral effects. However, these are apparent only when the animals are challenged with cocaine or MK-801, but not with amphetamine or morphine, or when drug-free. This suggests that the mPFC might have a special role in mediating cocaine and MK-801 effects.

Amphetamine↗

PubMed1997

Antiparkinsonian and other motor effects of flupirtine alone and in combination with dopaminergic drugs.

In this study we attempted to specify the behavioural profile of the analgesic flupirtine (1, 10 and 20 mg/kg p.o.) in the rat with respect to (i) its antiparkinsonian potential alone and as an adjunct to L-dihydroxyphenylalanine (L-DOPA) in the haloperidol-induced catalepsy (0.5 mg/kg haloperidol i.p.), (ii) locomotion and exploratory behaviour in the open field with holeboard, and (iii) possible psychomotor stimulating effects in the experimental chamber. In the two latter tests, behaviour was additionally challenged by D-amphetamine (2 mg/kg i.p.). In the catalepsy tests (horizontal bar, podium, grid) flupirtine alone was anticataleptic at doses of 10 and 20 mg/kg p.o., and the antiparkinsonian potential of a subthreshold dose of L-DOPA (50 mg/kg p.o.) was potentiated by 1 and 10 mg/kg p.o. flupirtine. On spontaneous forward locomotion in the open field with holeboard, flupirtine (1 and 10 mg/kg p.o.) had no marked effect but increased the frequency and duration of head dips, indicative for augmenting exploratory behaviour. Spontaneous rearing was reduced and D-amphetamine-induced rearing was enhanced by 1 mg/kg p.o. flupirtine. Grooming was reduced by 1 and 10 mg/kg p.o. flupirtine. In contrast, turning and grooming behaviour (spontaneous as well as D-amphetamine-induced) was not markedly influenced by flupirtine in the experimental chamber. Sniffing was increased in this test by 1 mg/kg p.o. flupirtine but not by the higher dose. Flupirtine is highly effective in antagonising neuroleptic-induced catalepsy as well as in potentiating L-DOPA treatment in the rat, suggesting it is a prospective new candidate for the therapy of Parkinson's disease.

Aminopyridines↗

PubMed1997

6-Hydroxydopamine lesion of locus coeruleus and the antiparkinsonian potential of NMDA-receptor antagonists in rats.

Behavioral and neurochemical effects after bilateral 6-hydroxy-dopamine locus coeruleus- (LC) lesion were examined in rats and compared to sham-lesioned controls. Behavior after treatment with the antiakinetic drugs dizocilpine, amantadine, memantine or L-DOPA as well as joint treatment of these drugs with haloperidol were tested in an open field with holeboard and in an experimental chamber. Under saline spontaneous activity (open field with holeboard) and sniffing (experimental chamber) were reduced after lesion. Injection of the proparkinsonian drug haloperidol decreased sniffing in all rats but to a greater extent in LC-lesioned rats. In combination with haloperidol none of the tested drugs could completely compensate for the motor deficits induced by the lesion. Neurochemical data revealed a reduced content of noradrenaline in the prefrontal cortex and in the posterior striatum of LC-lesioned rats. These results indicate that loss of LC neurons intensifies parkinsonian symptoms induced by blockade of dopamine D2-receptors, and lowers the antiakinetic potential of dizocilpine, amantadine, memantine or L-DOPA.

Adrenergic Agents↗

PubMed1997

Behavioural pharmacology of the non-competitive NMDA antagonists dextrorphan and ADCI: relations between locomotor stimulation, anticataleptic potential and forebrain dopamine metabolism.

The effects of systemic administration of the non-competitive N-methyl-D-aspartate (NMDA) antagonists dextrorphan (10-40 mg/kg, i.p.) and [+/-]-5-aminocarbony-10,11-dihydro-5H-dibenzo[a,d]cycloheptan++ +-5,10-imine (ADCI) (25-70 mg/kg, i.p.) on basal ganglia-mediated behaviour and on forebrain dopamine metabolism were investigated in rats. Dextrorphan increased locomotor activity but did not induce stereotyped sniffing. ADCI failed to produce any significant motor stimulant and motor depressant actions. Both dextrorphan and ADCI dose-dependently antagonized catalepsy induced by the D-1 dopamine receptor antagonist SCH 23390 or the D-2 dopamine receptor antagonist haloperidol. Only the highest doses of dextrorphan and ADCI increased dopamine metabolism in the prefrontal cortex and/or in the nucleus accumbens, but not in the dorsal striatum. Our results show that dextrorphan and ADCI produce some of the behavioural effects (antagonism of experimentally induced catalepsy) and neurochemical actions (regionally selective stimulation of dopamine metabolism) that have previously been observed in the prototypical non-competitive NMDA antagonist, dizocilpine. The failure of ADCI to induce hyperlocomotion and stereotypy suggests that anticataleptic doses of ADCI may be devoid of the psychotomimetic actions commonly associated with non-competitive blockade of NMDA receptor function.

Animals↗

PubMed1997

Aminoadamantanes as NMDA receptor antagonists and antiparkinsonian agents--preclinical studies.

Aminoadamantanes such as 1-aminoadamantane (amantadine) and 1-amino-3,5-dimethyladamantane (memantine) are N-methyl-D-aspartate (NMDA) receptor antagonists which show antiparkinsonian-like activity in animal models and in Parkinson's patients. The issue of whether NMDA antagonism plays a role in the symptomatological antiparkinsonian activity of amantadine and memantine is addressed by comparing: behaviourally effective doses, serum/brain levels, and their potency as NMDA receptor antagonists. In the case of memantine, blockade of NMDA receptors is probably the only mechanism responsible for antiparkinsonian activity, whereas for amantadine the situation is clearly far more complex. There are a number of differences between memantine and amantadine both in vitro and in vivo, and although NMDA receptor antagonism certainly participates in the antiparkinsonian activity of amantadine, other effects, some of which are elusive, also play a role. Moreover, it has been suggested that the pathomechanism of Parkinson's disease involves excitotoxic processes and that treatment with NMDA receptor antagonists might also slow the progression of neurodegeneration. If this claim is true, such an effect could be achieved with amantadine and memantine which show neuroprotective activity in animals at therapeutically relevant doses.

Amantadine↗

PubMed1997

Behavioural pharmacology of glutamate receptors in the basal ganglia.

Glutamate receptors play a major role in the transmitter balance within the basal ganglia (BG). N-methyl-D-aspartate (NMDA) receptor stimulation within the striatum acts behaviourally depressant while intrastriatal as well as systemic administration of NMDA receptor-antagonists have rather stimulatory effects despite the different profiles of non-competitive-, competitive NMDA receptor- and glycine site-antagonists. In animal models of Parkinson's disease all these NMDA receptor antagonists counteract parkinsonian symptoms or act synergistically with L-3,4-dihydroxyphenylalanine (L-DOPA). The strong locomotion-inducing effect of the non-competitive NMDA receptor antagonists is partly, but not fully, mediated by a dopamine (DA) release in the nucleus accumbens. Manipulations at alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors produce poor behavioural effects. These, however, are different or even opposed to NMDA receptor mediated effects. Local infusions of AMPA receptor-antagonists into the BG output nuclei have an anti-parkinsonian effect but systemic injections are ineffective. These drugs even counteract the anti-parkinsonian effect of DA agonists and of non-competitive NMDA receptor antagonists as well as the DA releasing effects of the latter drugs. Only few data on the role of metabotropic receptors exist but the different receptor subtypes with different regional distribution represent a promising target for pharmacological interventions.

Animals↗

PubMed1997

Interactions of MK-801 and GYKI 52466 with morphine and amphetamine in place preference conditioning and behavioural sensitization.

In an earlier study we showed that co-administration of the NMDA-receptor antagonist MK-801 during conditioning sessions blocks morphine-induced conditioned place preference (CPP). From this result, the question arose of whether this blockade is due to state-dependency effects induced by MK-801. Therefore, in a first experiment, animals were tested in the drugged state under which they had been conditioned. These animals did not show a CPP, thus it can be concluded that MK-801 does not make state-dependent the morphine conditioning. In the same experiment those animals receiving only morphine during conditioning sessions showed a significant CPP when tested in an undrugged state but failed to show CPP when tested after injection of MK-801 (i.e., in the drugged state). These results indicate that MK-801 not only blocks the development of morphine-induced CPP but is also able to block the expression of a conditioned response that has been acquired before. In the same experiment repeated injection of neither morphine nor MK-801 produced sensitized locomotor activity. However, a strong sensitization was observed following repeated injection of morphine plus MK-801. There was also cross-sensitization between morphine plus MK-801 and MK-801 alone but not with morphine alone, and also between morphine and MK-801, but not vice versa. In a second experiment the effects of the AMPA-receptor antagonist GYKI 52466 were examined. It was found that GYKI 52466 did not produce CPP or behavioural sensitization. Finally, in a third experiment, CPP was induced by morphine and amphetamine (animals tested in the drug-free state), and behavioural sensitization was induced by amphetamine. When animals were tested after an injection of GYKI 52466, neither the morphine- nor the amphetamine-conditioned animals showed a CPP. Likewise, challenge of sensitized animals with amphetamine plus GYKI 52466 failed to produce a sensitized response. It can be concluded, that GYKI 52466, like MK-801, can block the expression of a conditioned response, and can also block the expression of sensitized behaviour.

Amphetamine↗

PubMed1997

Recurrence of haemolytic-uraemic syndrome in renal transplants: a single-centre report.

BACKGROUND: The incidence of recurrence of haemolytic-uraemic syndrome (HUS) in renal allografts appears to vary by centre, with the highest rates reported from the University of Minnesota. It is possible that the high rate of HUS recurrence at this institution reflects a transplant population skewed towards patients with a form of HUS that is more likely to recur in the allograft. METHODS: This study examined whether the initial episode of HUS in the native kidneys was preceded by a diarrhoeal prodrome ('classical HUS') or not ('atypical HUS'), and evaluated transplant outcomes in 24 patients who received 36 transplants at the University of Minnesota between 31 May 1972 and 31 December 1994. RESULTS: Eighteen of the 24 patients had atypical HUS, three had classical HUS, and in three patients the presence or absence of a diarrhoeal prodrome could not be determined. Recurrent HUS, defined as microangiopathic haemolytic anaemia, thrombocytopenia, renal insufficiency, and allograft biopsy findings compatible with HUS, occurred 16 times in 14 grafts in 11 patients. Nine of these patients had atypical HUS, one had classical HUS, and in one the nature of the prodrome could not be determined. Eleven of the 14 initial recurrences took place within 2 months of transplant. Recurrence was not more frequent in patients who received cyclosporin or antilymphocyte preparations. Actuarial analysis using matched controls showed poorer graft survival in patients with a primary diagnosis of HUS (P = 0.007), due to the high frequency of graft loss in HUS patients with recurrence. CONCLUSION: Based upon these data and a review of the literature, it can be concluded that the risk of recurrence of HUS in the allograft is confined almost entirely to patients with atypical forms of HUS.

Adolescent↗

PubMed1996

1S,3R-ACPD has cataleptogenic effects and reverses MK-801-, and less pronounced, D,L-amphetamine-induced locomotion.

The purpose of this study was to examine the motor effects of (1S,3R)-1-amino-cyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD), an agonist at metabotropic glutamate receptors, its interaction with dizocilpine (MK-801), a NMDA receptor antagonist, and with D,L-amphetamine, an indirect dopamine receptor agonist. 1S,3R-ACPD (20, 30, 40, 80 micrograms) evoked prominent locomotor and exploratory deficits in an open-field hole-board test and a moderate akinesia and rigidity in a catalepsy test (30, 40, 80 micrograms). MK-801 (0.08, 0.16, 0.32 mg/kg i.p.) as well as D,L-amphetamine (1.0, 2.0, 3.0 mg/kg i.p.) potently reversed 1S,3R-ACPD-induced (80 micrograms) catalepsy. MK-801 and D,L-amphetamine, administered alone, induced motor stimulation. 1S,3R-ACPD (80 micrograms) reversed the effects of the two lower doses of MK-801. 1S,3R-ACPD reversed D,L-amphetamine-induced motor stimulation to a minor extent than that of MK-801. Thus motor deficits induced by 1S,3R-ACPD were reversed by both, NMDA receptor blockade and dopamine receptor activation. 1S,3R-ACPD reversed motor stimulation, induced by NMDA receptor blockade and, however less pronounced, that by dopamine receptor activation.

Amphetamine↗