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  • 1
    Electronic Resource
    Electronic Resource
    Regional cerebral blood flow in IDDM patients: Effects of diabetes and of recurrent severe hypoglycaemia (1994)
    Springer
    Diabetologia 37 (1994), S. 257-263 
    Details
    ISSN: 1432-0428
    Keywords: Diabetes mellitus ; hypoglycaemia ; cerebral blood flow ; SPECT
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Chronic hyperglycaemia and recurrent severe hypoglycaemia have both been implicated as causing cerebral damage in patients with diabetes. Although cognitive dysfunction and intellectual impairment have been demonstrated in patients with recurrent severe hypoglycaemia, structural correlates have not been described, and it is not known whether specific functional changes occur in the brains of affected patients. Regional cerebral blood flow was estimated by SPECT with 99mTechnetium Exametazime in 20 patients with IDDM. Ten patients had never experienced severe hypoglycaemia and 10 had a history of recurrent severe hypoglycaemia. Patient results were compared with 20 age- and sex-matched healthy volunteers. We observed differences between the two patient groups and the control group. Tracer uptake was greater in diabetic patients in the superior pre-frontal cortex. This effect was particularly pronounced in the group who had a history of previous severe hypoglycaemia. Patients with a history of recurrent hypoglycaemia also had a relative reduction in tracer uptake to the calcarine cortex. This suggests an alteration in the pattern of baseline regional cerebral blood flow in diabetic patients with frontal excess and relative posterior reduction in cerebral blood flow.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00398052
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  • 2
    Electronic Resource
    Electronic Resource
    Regional cerebral blood flow in IDDM patients: effects of diabetes and of recurrent severe hypoglycaemia (1994)
    Springer
    Diabetologia 37 (1994), S. 257-263 
    Details
    ISSN: 1432-0428
    Keywords: Key words Diabetes mellitus, hypoglycaemia, cerebral blood flow, SPECT.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Chronic hyperglycaemia and recurrent severe hypoglycaemia have both been implicated as causing cerebral damage in patients with diabetes. Although cognitive dysfunction and intellectual impairment have been demonstrated in patients with recurrent severe hypoglycaemia, structural correlates have not been described, and it is not known whether specific functional changes occur in the brains of affected patients. Regional cerebral blood flow was estimated by SPECT with 99mTechnetium Exametazime in 20 patients with IDDM. Ten patients had never experienced severe hypoglycaemia and 10 had a history of recurrent severe hypoglycaemia. Patient results were compared with 20 age- and sex-matched healthy volunteers. We observed differences between the two patient groups and the control group. Tracer uptake was greater in diabetic patients in the superior pre-frontal cortex. This effect was particularly pronounced in the group who had a history of previous severe hypoglycaemia. Patients with a history of recurrent hypoglycaemia also had a relative reduction in tracer uptake to the calcarine cortex. This suggests an alteration in the pattern of baseline regional cerebral blood flow in diabetic patients with frontal excess and relative posterior reduction in cerebral blood flow. [Diabetologia (1994) 37: 257–263]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00398052
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  • 3
    Electronic Resource
    Electronic Resource
    Effects of glucocorticoids on 5-HT1A presynaptic function in the mouse (1994)
    Springer
    Psychopharmacology 114 (1994), S. 360-364 
    Details
    ISSN: 1432-2072
    Keywords: Corticosterone ; Corticosteroid receptor ; 8-OH-DPAT ; Hypothermia ; 5-HT1A receptor ; 5-Hydroxytryptophan
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract 8-OH-DPAT, a selective 5-HT1A agonist, produced a hypothermic response in mice at a dosage of 0.5 mg/kg. Administration of corticosterone-21-acetate (0.5, 5 and 50 mg/kg, daily for 3 and 10 days) produced a dose-dependent attenuation of this hypothermic response in mice. When all controls and corticosterone treated mice were retested, 14 days after initial testing, they did not differ in the hypothermic responses induced by 8-OH-DPAT. Mice treated with aldosterone (50 mg/kg), dexamethasone (50 mg/kg) and the specific type 2 corticosteroid receptor agonist, 11b,17b-dihydroxy-21-methyl-17a-pregna-1,4,6-trien-20-yn-3-one (RU26988, 30 mg/kg) for 10 days, did not differ from vehicle treated controls in the hypothermic response to 8-OH-DPAT. Mice administered corticosterone-21-acetate (30 mg/kg, daily) for 10 days displayed a motor behavioural syndrome, which was not seen in controls, when injected with 5-hydroxytryptophan (5-HTP, 100 mg/kg) 15 min after the injection of carbidopa (25 mg/kg). This was significantly decreased by pretreatment with the 5-HT1A receptor antagonist 1-(2-methoxyphenyl)-4-(4-phthalimidobutyl)-piperazine (NAN-190 5 mg/kg, 30 min prior to administration of carbidopa). Taken together, this evidence is compatible with a specific corticosterone induced facilitation of 5-HT release due to attenuation of inhibitory 5-HT1A autoreceptor function.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02244859
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  • 4
    Electronic Resource
    Electronic Resource
    The pharmacology of the behavioral and hypothermic responses of rats to 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) (1987)
    Springer
    Psychopharmacology 91 (1987), S. 506-511 
    Details
    ISSN: 1432-2072
    Keywords: 8-OH-DPAT ; 5-Hydroxytryptamine (5-HT) ; 5-HT1 receptor ; Parachlorophenylalanine (PCPA) ; Clenbuterol ; Quipazine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The hypothermic and motor behavioural responses to 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) have been investigated in the rat. The dose-effect relationship showed that hypothermia appeared at a lower dose than a definite motor syndrome. The hypothermic response to 8-OH-DPAT was attenuated following depletion of 5-hydroxytryptamine (5-HT) by repeated intraperitoneal (IP) administration of parachlorophenylalanine (200 mg/kg) or by injection of 5,7-dihydroxytryptamine (5,7-DHT, 100 μg) into the region of the third ventricle; the motor behavioural response produced simultaneously was not. Indeed, after 5,7-DHT, it was increased. Quipazine (1 mg/kg, IP) antagonised the hypothermic response and facilitated the motor behaviour. Clenbuterol (2.5 mg/kg, IP) increased both hypothermic and motor responses. (±)-propranolol was without effect on the simple hypermotility produced by 8-OH-DPAT, although it is known to antagonise the hypothermic and stereotyped motor responses. It is concluded that 8-OH-DPAT probably produces its hypothermic effects by actions at 5-HT receptors located presynaptically on 5-HT neurones, while the stereotyped components of the serotonin syndrome appear to be mediated by post-synaptic receptors.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00216019
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  • 5
    Electronic Resource
    Electronic Resource
    Attenuation by electroconvulsive shock and antidepressant drugs of the 5-HT1A receptor-mediated hypothermia and serotonin syndrome produced by 8-OH-DPAT in the rat (1987)
    Springer
    Psychopharmacology 91 (1987), S. 500-505 
    Details
    ISSN: 1432-2072
    Keywords: 5-Hydroxytryptamine (5-HT) ; 5-HT1A receptor ; Electroconvulsive shock ; Antidepressants ; 8-OH-DPAT ; Zimeldine ; Desipramine ; Tranylcypromine ; Flurazepam
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The hypothermia and motor behavioural syndrome produced in rats by injection of the 5-HT1A ligand 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) has been studied following administration of electroconvulsive shock under halothane anaesthesia (ECS) and during the administration of antidepressant drugs. Repeated ECS attenuated the hypothermic response to 8-OH-DPAT (0.1 mg/kg SC) immediately after the last of five shocks given spread out over 10 days with a maximal effect 21 days after the final shock. A single ECS was without effect. The serotonin syndrome produced by 8-OH-DPAT (0.75 mg/kg SC) was also attenuated, although simple motility was increased. Zimeldine (20 mg/kg) and desipramine (20 mg/kg), when given once daily for 14 days also attenuated the hypothermia and the serotonin syndrome provoked by 8-OH-DPAT. The hypothermic response was somewhat reduced 24 h after a single injection of zimeldine but not 45 min after zimeldine (5 mg/kg IP). At a high dose (20 mg/kg) tranylcypromine clearly attenuated both responses 24 h after a single injection. Tranylcypromine (6 mg/kg IP) showed a smaller effect after a single injection but attenuated the behavioural syndrome on repeated administration. Repeated injection of flurazepam (10 mg/kg IP) was without effect on either the behavioural or hypothermic response to 8-OH-DPAT. These findings are consistent with the view that responses mediated via the 5-HT1A receptor may be involved in the mechanism of action of antidepressant treatments.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00216018
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  • 6
    Electronic Resource
    Electronic Resource
    Review of the pharmacology and clinical pharmacology of 3,4-methylenedioxymethamphetamine (MDMA or “Ecstasy”) (1995)
    Springer
    Psychopharmacology 119 (1995), S. 247-260 
    Details
    ISSN: 1432-2072
    Keywords: 3,4-Methylenedioxymethamphetamine ; MDMA ; Ecstasy ; 5-Hydroxytryptamine ; Hyperthermia ; Neurotoxicity ; Neuroleptics ; Chlormethiazole
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract 3,4-Methylenedioxymethamphetamine (MDMA or “Ecstasy”) was first synthesised 80 years ago, but has recently received prominence as an illegally synthesised recreational drug of abuse. There is a widely held belief among misusers that it is safe. In the last 2–3 years there have been a number of reports of the drug producing severe acute toxicity and death and there are concerns that it may cause long term toxic damage to 5-hydroxytryptamine (5-HT) nerve terminals. There is a considerable literature on the acute pharmacological effects of MDMA in experimental animals, and this is reviewed. The drug produces both hyperthermia and the “serotonin syndrome”, a series of behavioural changes which result from increased 5-HT function. Acute clinical toxicity problems following MDMA ingestion also include hyperthermia and the appearance of the serotonin syndrome. The hyperthermia appears to precipitate other severe clinical problems and the outcome can be fatal. In agreement with others, we suggest that the recent increase in the number of reports of MDMA toxicity probably results from the widespread use of the drug at all night dance parties or “raves”. The phenomenon of amphetamine aggregation toxicity in mice was reported 40 years ago. If applicable to MDMA-induced toxicity in humans, all the conditions necessary to induce or enhance toxicity are present at raves: crowded conditions (aggregation), high ambient temperature, loud noise and dehydrated subjects. Administration of MDMA to rodents and non-human primates results in a long term neurotoxic decrease in 5-HT content in several brain regions and there is clear biochemical and histological evidence that this reflects neurodegeneration of 5-HT terminals. Unequivocal data demonstrating that similar changes occur in human brain do not exist, but limited and indirect clinical evidence gives grounds for concern. There are also data suggesting that long term psychiatric changes can occur, although there are problems of interpretation and these are reviewed. Suggestions for the rational treatment of the acute toxicity are made on the basis of both pharmacological studies in animals and current clinical practice. Cases presenting clinically are usually emergencies and unlikely to allow carefully controlled studies. Proposals include decreasing body temperature (possibly with ice), the use of dantrolene and anticonvulsant and sedative medication, particularly benzodiazepines. The use of neuroleptics requires care because of the theoretical risk of producing the neuroleptic malignant syndrome and the possibility of precipitating seizures. In rats, chlormethiazole antagonises the hyperthermia produced by MDMA and has been shown clinically to block MDMA-induced convulsive activity.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02246288
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  • 7
    Electronic Resource
    Electronic Resource
    The effects of a 5-HT1 receptor ligand isapirone (TVX Q 7821) on 5-HT synthesis and the behavioural effects of 5-HT agonists in mice and rats (1986)
    Springer
    Psychopharmacology 89 (1986), S. 382-387 
    Details
    ISSN: 1432-2072
    Keywords: 5-HT1 antagonist ; 5-HT1A receptor function ; 5-HT1B receptor function ; TVX Q 7821 ; 5-HT2 receptor function ; 5-HT-mediated behaviour ; Isapirone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of 2-(4-(4-(2-pyrimidinyl)-1-piperazinyl)-butyl)-1,2-benzoisothiazol-3(2H)one-1,1-dioxide hydrochloride (isapirone, TVX Q 7821), a putative 5-HT1 receptor antagonist, has been studied on various models of 5-HT receptor sub-type function. In mice TVX Q 7821 produced a dose-dependent inhibition of the hypothermia induced by 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) with an ED50 of 5.3 mg/kg suggesting that TVX Q 7821 was an antagonist of the presynaptic (possibly somato-dendritic) 5-HT1A receptor. TVX Q 7821 did not alter the locomotor response to the suggested 5-HT1B agonist RU 24969. The rate of mouse brain 5-HT synthesis was accelerated by TVX Q 7821 (10 mg/kg). 5-HT2 receptor-mediated head twitch behaviour induced by precursor loading with 5-HTP was unaffected by TVX Q 7821 (10 mg/kg) pretreatment 75 min earlier, but the head-twitch induced by the agonist 5-methoxy-N,N-dimethyltryptamine was enhanced by prior treatment with TVX Q 7821. In rats the hypothermia induced by 8-OH-DPAT was partially antagonised by TVX Q 7821 while the behavioural “serotonin syndrome” induced by 8-OH-DPAT (a possible post-synaptic 5-HT1B-mediated effect) was unaffected by TVX Q 7821 as was the locomotion induced by RU 24969. The data suggest that TVX Q 7821 is a good presynaptic 5-HT1A antagonist in mice, as indicated by the 8-OH-DPAT-induced hypothermia and 5-HT synthesis rate studies. It did not antagonise 5-HT1B-mediated behaviour in mice or rats and appeared to have an antagonist action at pre- but not post-synaptic 5-HT1A receptors in rats.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00174379
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  • 8
    Electronic Resource
    Electronic Resource
    Lithium decreases 5-HT1A and 5-HT2 receptor and α2-adrenoreceptor mediated function in mice (1986)
    Springer
    Psychopharmacology 90 (1986), S. 482-487 
    Details
    ISSN: 1432-2072
    Keywords: Lithium ; 5-Hydroxytryptamine ; 5-HT1 receptor ; 5-HT2 receptor ; a 2-Adrenoceptor ; 8-OH-DPAT ; Clonidine ; Mouse
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Lithium administration (LiCl, 10 mmol/kg, SC on day 1, followed by 3 mmol/kg twice daily subsequently) for 14 days to mice produced attenuation of the hypothermic response to injection of 8-hydroxy-2-(di-n-propyla-mino)tetralin (8-OH-DPAT, 0.5 mg/kg SC). Head twitch responses to the 5-HT-receptor agonist 5-methoxy-N,N-dimethyltryptamine (2.5 mg/kg IP) and to precursor loading with carbidopa (25 mg/kg, IP) and 5-hydroxytryptophan (100 mg/kg IP) were similarly attenuated. By contrast with this reduction of 5-hydroxytryptamine (5-HT) function mediated by the 5-HT1A and 5-HT2 receptor sub-types, repeated lithium administration had no effect on the motor response to a putative 5-HT1B receptor agonist 5-methoxy-3(1,2,3,6-tetrahydropyridin-4-yl)1H indole (RU 24969, 3 mg/kg IP). Alpha2 adrenoceptor function, assessed by the sedation response to clonidine (0.25 mg/kg, IP), was also attenuated by repeated lithium administration. It is proposed that these actions may explain the emergence of lithium as an adjunct to the treatment of refractory depressive illness.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00174065
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  • 9
    Electronic Resource
    Electronic Resource
    The enhancement by lithium of the 5-HT1A mediated serotonin syndrome produced by 8-OH-DPAT in the rat: evidence for a post-synaptic mechanism (1986)
    Springer
    Psychopharmacology 90 (1986), S. 488-493 
    Details
    ISSN: 1432-2072
    Keywords: Lithium ; 5-Hydroxytryptamine ; 5-HT1 receptor ; 8-OH-DPAT ; P-Chlorophenylanine ; 5-HT-mediated behaviour ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Administration of lithium chloride (10 mmol/kg on day 1 and 3 mmol/kg twice daily on subsequent days, SC) for 3–14 days enhances the components of the serotonin syndrome produced by 8-hydroxy-2-(di-propylamino)tetralin (8-OH-DPAT) in the rat. The hypothermic response produced simultaneously was unaltered. Following lithium administration for 3 days the motor response to 5-methoxy,N,N-dimethyltryptamine was also facilitated. These data suggest that lithium administration enhances post-synaptic 5-HT receptor-mediated behavioural responses. (−)-Propranolol (20 mg/kg, IP) but not (+)-propranolol (20 mg/kg IP) fully antagonised the facilitated response to 8-OH-DPAT seen following lithium administration; ritanserin (200 μg/kg, IP) was without effect. These findings favour a mechanism for the action of lithium involving the 5-HT1A receptor. Depletion of 5-hydroxytryptamine (5-HT) with parachlorophenylalanine (PCPA, 300 mg/kg, IP on day 1 and 2 of lithium administration) did not prevent the facilitation by lithium of the response to 8-OH-DPAT. These data strengthen the suggestion that lithium has its effect on 5-HT1A-mediated motor function by a post-synaptic action. By contrast, motor responses to the putative 5-HT1B receptor agonist 5-methoxy-3-(1,2,3,6-tetrahydro-pyridin-4-yl)-1H-indole (RU 24969) were unaltered by repeated lithium administration.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00174066
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  • 10
    Electronic Resource
    Electronic Resource
    Effects of a single dose of the acetylcholinesterase inhibitor velnacrine on recognition memory and regional cerebral blood flow in Alzheimer's disease (1992)
    Springer
    Psychopharmacology 108 (1992), S. 103-109 
    Details
    ISSN: 1432-2072
    Keywords: Dementia ; Alzheimer's disease ; Acetylcholinesterase-inhibitor ; Tomography, single photon emission computed ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of a single oral dose of the acetylcholinesterase inhibitor velnacrine maleate on word and object recognition memory and regional uptake of99mTc-exametazime were examined in patients with Alzheimer's disease. Word recognition memory was marginally improved 2 h after 75 mg velnacrine. With the same dose of velnacrine a relative increase in superior frontal uptake of99mTc-exametazime was shown with single photon emission computed tomography (SPECT). This suggests increased regional perfusion and metabolism as a consequence of cholinergic stimulation. The effect did not co-vary with the degree of memory improvement, but, instead, more cognitively impaired patients showed a greater increase in tracer uptake after velnacrine, suggesting cholinergic hypersensitivity in the brains of Alzheimer patients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02245293
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