G Curzon

University of London, Londinium, England, United Kingdom

Are you G Curzon?

Claim your profile

Publications (199)1268.56 Total impact

  • Annals of the New York Academy of Sciences 12/2006; 473(1):549 - 552. DOI:10.1111/j.1749-6632.1986.tb23657.x · 4.31 Impact Factor
  • K E Heslop, G Curzon
    [Show abstract] [Hide abstract]
    ABSTRACT: Rats were given a single dose of reserpine (5 mg/kg s.c.) and behavioural responses to agonists at 5-HT receptor subtypes compared with those of control animals 21 days later. The following effects of activating postsynaptic 5-HT1A receptors by the agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) were significantly increased: tail-flick, reciprocal forepaw treading, flat body posture. The hyperphagic effect of activating presynaptic 5-HT1A receptors by 8-OH-DPAT tended to increase and hypothermia on activating postsynaptic 5-HT1A sites tended to decrease. The hyperlocomotor effect of activating 5-HT1A sites also tended to decrease possibly as a result of a dependence of this response on the known depletion of catecholamines by reserpine. Head shakes on activating 5-HT2A receptors by 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) and two effects of activating 5-HT2C receptors by 1-(3-chlorophenyl) piperazine (mCPP) were significantly increased (hypophagia, anxiety) and a third effect, hypolocomotion tended to increase but hypophagia on activating postsynaptic 5-HT1B receptors by CP-94, 253 was significantly attenuated. The results are discussed with particular reference to altered 5-HT function in depression.
    Neuropharmacology 07/1999; 38(6):883-91. DOI:10.1016/S0028-3908(99)00002-7 · 4.82 Impact Factor
  • G Curzon, E L Gibson
    [Show abstract] [Hide abstract]
    ABSTRACT: Medical and social pressures have led to increased emphasis on dieting. However, there has been a concurrent world wide increase of obesity. Therefore, much attention has been paid to the development of drugs which decrease appetite. The most extensively used drug of this type over the past three decades has been the serotonergic compound fenfluramine. Recent findings have cast doubt on the previously accepted view that its action requires the release of central 5-HT. Instead, it seems likely that action on specific 5-HT receptors independently of 5-HT stores is involved. It is ironic that these new developments in understanding its mechanism of action have coincided with the recognition of its cardiovascular side-effect apparent especially in patients treated with d-fenfluramine combined with phentermine. This has forced the withdrawal of fenfluramine (both as racemate and d-isomer) from clinical use. The implications of these developments are commented upon.
    Advances in Experimental Medicine and Biology 02/1999; 467:95-100. · 2.01 Impact Factor
  • A O Oluyomi, K P Datla, G Curzon
    [Show abstract] [Hide abstract]
    ABSTRACT: The effects of the (+) and (-) enantiomers of the antidepressant drug tianeptine (5, 10, 20 mg/kg, i.p.) on wet dog shakes (WDS) and faecal pellet production induced by concurrently administered 5-hydroxytryptophan (5-HTP, 100 mg/kg, i.p.) given 30 min after carbidopa (25 mg/kg, i.p.) were investigated in rats. WDS scores peaked approximately 1 hr after giving 5-HTP and gradually declined over the next 2 hr. (-)-Tianeptine dose-dependently and significantly inhibited WDS. Inhibition became less marked with time after administration, but remained significant over the 3 hr period after the 10 and 20 mg/kg doses and during the first 40 min after the 5 mg/kg dose. (+)-Tianeptine caused slight inhibition without dose-dependence and slightly increased net inhibition when added to the (-) isomer (10 mg/kg). The induction of faecal pellet production by 5-HTP was significantly and dose-dependently inhibited by (-)-tianeptine. The (+) isomer neither altered this effect of 5-HTP nor its inhibition by (-)-tianeptine. Results show that inhibition of 5-HTP-induced WDS and faecal pellet formation by tianeptine was almost completely dependent on the (-) isomer.
    Neuropharmacology 04/1997; 36(3):383-7. DOI:10.1016/S0028-3908(97)00016-6 · 4.82 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Acute (10mg/kg, i.p.) and chronic (10mg/kg/day, i.p. for 10 days) diazepam treatments decreased hippocampal dialysate 5-HT (but not 5-HIAA) concentrations in freely moving rats, suggesting decreased availability of 5-HT to receptors. Twenty-four hours after the last chronic diazepam injection, hippocampal dialysate 5-HT did not differ from that in vehicle-treated rats. However, although reduced 5-HT availability often increases postsynaptic 5-HT receptor-mediated responses, the anxiogenic effect of m-chlorophenylpiperazine (mCPP), which is mediated by the activation of postsynaptic 5-HT(2C) receptors, was not increased (as indicated by the elevated plus-maze test) when given 2 days after 10 days of chronic diazepam, in intact rats. Nevertheless, concurrently in that test, significantly increased anxiety occurred after withdrawal from chronic diazepam (10mg/kg/day x 10 days). The results suggest that benzodiazepine withdrawal-induced anxiety is not mediated by changes in 5-HT(2C) receptor sensitivity, and may be independent of the benzodiazepine-induced reduction of 5-HT release in the rat hippocampus.
    Behavioural pharmacology 04/1996; 7(2):185-193. DOI:10.1097/00008877-199603000-00009 · 2.19 Impact Factor
  • K P Datla, G Curzon
    [Show abstract] [Hide abstract]
    ABSTRACT: The effects of p-chlorophenylalanine (PCPA, 100-150 mg/kg x 1. i.p.), doses which decrease brain 5-hydroxytryptamine (5-HT) by 30-50%, were investigated in both intact rats and 14 days after giving p-chloroamphetamine (PCA, 10 mg/kg/day x 2, i.p.). The PCPA dose-dependently decreased brain regional 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) 24 hr later. As per cent decreases of 5-HIAA were greater than those of 5-HT in cortex, striatum and hippocampus 5-HIAA/5-HT ratios fell, suggesting that partial inhibition of 5-HT synthesis by PCPA increases 5-HT conservation in these terminal regions. In the hypothalamus and brain stem, decreases of the ratio were small or absent. The PCA given without subsequent PCPA treatment decreased 5-HT and 5-HIAA so that 5-HT fell by about 70% in the cortex, striatum and hippocampus, 55% in the brain stem but only by 27% in the hypothalamus. The PCPA given after PCA decreased 5-HT and 5-HIAA further but not the 5-HIAA/5-HT ratios and increased the ratio in the brain stem. The 5-HIAA/5-HT findings imply that the increase of 5-HT conservation after PCPA treatment does not occur after partial depletion of 5-HT by PCA. The increase of the 5-HIAA/5-HT ratio in the brain stem is explicable by the resistance to both PCA and PCPA of 5-HT in cell bodies where the ratio is high. Results are discussed in relation to the question of whether the PCA treatment used destroys axon terminals projecting from the dorsal but not from the median raphe.
    Neuropharmacology 04/1996; 35(3):315-20. DOI:10.1016/0028-3908(96)00175-X · 4.82 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Rats were fed a control or vitamin E (all-rac-alpha-tocopheryl acetate)-deficient diet for 3 or 12 weeks. Serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), tryptophan, and alpha-tocopherol concentrations were determined in the frontal cortex using HPLC, alpha-Tocopherol concentrations fell significantly to 27% of control values at 12 weeks. Tissue 5-HT, 5-HIAA, and tryptophan concentrations were not significantly altered by the vitamin E-deficient diet at either time point. In vivo microdialysis revealed normal basal and K(+)-stimulated concentrations of 5-HT and 5-HIAA, but extracellular concentrations of tryptophan were significantly decreased after 3 weeks on the vitamin E-deficient diet, which resulted in an increase in the tissue/extracellular ratio and suggested a change in compartmentation. However, after 12 weeks on the deficient diet these values had returned to normal. Results in general indicate that a prolonged and substantial depletion of brain vitamin E can occur without major disturbance of serotonergic function.
    Journal of Neurochemistry 03/1996; 66(2):860-4. DOI:10.1046/j.1471-4159.1996.66020860.x · 4.24 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: 1-(3-Chlorophenyl)piperazine (mCPP) (0.125-1.0 mg/kg i.p.), previously shown to inhibit social interaction, dose-dependently reduced exploration of the open arms of an elevated plus-maze. These findings suggest anxiogenic properties. The effect of mCPP was more potently inhibited by 1-(1-naphthyl)piperazine than by ketanserin, indicative of its mediation via activation of 5-HT2C rather than 5-HT2A receptors. The 5-HT1B receptor agonist CGS 12066B did not antagonise the anxiety-like response to mCPP, and further reduced exploration at the highest dose tested (10 mg/kg i.p.). Depletion of serotonin (5-HT) by p-chlorophenylalanine (PCPA, 150 mg/kg/day x 3) did not prevent the response, although PCPA itself increased open arm exploration. The 5-HT1A/B and beta-adrenoceptor antagonist 1-propanolol (5 mg/kg i.p.) and the peripheral beta 1-receptor antagonist atenolol (20 mg/kg i.p.) showed no significant activity on the plus-maze either alone or against the anxiogenic effect of mCPP. These results indicate that mCPP induces anxiety in the rat in the elevated plus-maze primarily by stimulation of postsynaptic 5-HT2C receptors, and suggest that sympathomimetic effects of mCPP are not involved.
    Neuropharmacology 03/1994; 33(3-4):457-65. DOI:10.1016/0028-3908(94)90076-0 · 4.82 Impact Factor
  • K E Heslop, G Curzon
    [Show abstract] [Hide abstract]
    ABSTRACT: Reserpine (5 mg/kg s.c.) was given to rats kept under a reversed light-dark cycle and 5-hydroxytryptamine (5-HT) and 5-hydroxyindole acetic acid (5-HIAA) determined in frontal cortex tissue and dialysate at various times after drug treatment. The decline and return of spontaneous locomotor activity was also measured. Tissue 5-HT was depleted to 16% of control values 24 hr after drug administration and had recovered to 61% of control after 21 days. Locomotion was profoundly reduced by 7 hr after reserpine but had returned to normal at 4 days. Dialysate 5-HT, both basal and its rise on potassium (K+) stimulation, was reduced at 1, 7 and 21 days after reserpine but the K+ stimulated increases (as % of control) did not rise above % tissue repletion, thus providing evidence against increased mobilization of the transmitter from the partially repleted vesicular stores. However, at 1 day after reserpine, basal dialysate 5-HT was proportionately less reduced than tissue 5-HT suggesting that release from a reserpine insensitive (extravesicular) pool was more effective than from the vesicular pool. At this time, the K(+)-stimulated rise of dialysate 5-HT was proportionately more reduced than tissue 5-HT. By 21 days, values converged so that % changes of the 3 compartments were the same suggesting that at this time both basal and K+ stimulated dialysate 5-HT was essentially all derived from the vesicular pool.
    Neuropharmacology 03/1994; 33(3-4):567-73. DOI:10.1016/0028-3908(94)90088-4 · 4.82 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The effect of a previous K+ stimulation on striatal extracellular monoamine levels during global ischaemia, under simulated penumbral conditions, was investigated. Rats were implanted with microdialysis probes in both striata, monoamine release was stimulated unilaterally by adding K+ (100 mM, 20 min) to the artificial CSF perfused through one probe, and bilateral partial ischaemia was imposed after monoamine levels had returned to basal values or below. Resultant increases in dialysate levels of dopamine and 5-hydroxytryptamine were markedly and significantly greater on the side previously exposed to K+, even though electrophysiological measurements indicated similarly severe ischaemia on both sides. Associated monoamine metabolite changes did not differ significantly between the two sides. There was no evidence of greater neuronal loss in the K(+)-stimulated striata 7 days after ischaemia. However, striatal tissue probably exposed to the highest concentrations of K+ could not be examined because of extensive gliosis around the probe.
    Journal of Neurochemistry 01/1994; 61(6):2233-8. DOI:10.1111/j.1471-4159.1993.tb07464.x · 4.24 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: We have measured changes in the levels of dopamine (DA), 5-hydroxytryptamine (5-HT), and their metabolites in striatal dialysates during 30 min of global ischaemia under simulated penumbral conditions, and compared these with neurological assessments over the following 7 days and histological damage at the end of this period. On the basis of dialysate DA levels during ischaemia, the animals fell into two subgroups; group I, with little or no DA increase (less than three times basal); and group II, with a much larger increase (greater than 30 times basal). Changes in 5-HT, though of lesser magnitude, showed a similar pattern. These findings may indicate that the amine changes depend on a critical reduction of blood flow within the range obtained by our experimental procedure. Levels of deaminated metabolites fell in all ischaemic animals, with comparable decreases of 3,4-dihydroxyphenylacetic acid plus homovanillic acid in both groups. Decreases of 5-hydroxyindoleacetic acid were greater in group II than in group I, but the relative differences between the groups were much less marked than those of 5-HT. These neurochemical findings suggest that moderate ischaemia affects extracellular amine and deaminated metabolite levels by different mechanisms. Only one of the ischaemic rats (a member of group II) showed a marked neurological deficit, but histological damage, as indicated by neuronal loss and gliosis in vulnerable structures, was apparent in all ischaemic animals. Although damage tended to be greater in animals with marked increases in extracellular monoamines, differences were not significant.(ABSTRACT TRUNCATED AT 250 WORDS)
    Journal of Neurochemistry 12/1993; 61(5):1801-7. DOI:10.1111/j.1471-4159.1993.tb09819.x · 4.24 Impact Factor
  • K P Datla, G Curzon
    [Show abstract] [Hide abstract]
    ABSTRACT: The effects of the novel antidepressant tianeptine on behaviours induced by the serotonin (5-HT) precursor 5-hydroxytryptophan (5-HTP) and the 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT) were investigated. Tianeptine (10 mg/kg, i.p.) significantly attenuated wet dog shakes (WDS) induced by 5-HTP (75 mg/kg, i.p.; 30 min after carbidopa 25 mg/kg, i.p.). The effect was most marked when 5-HTP and tianeptine were given together. The main metabolite of tianeptine also attenuated WDS. Components of the 5-HT syndrome (i.e. reciprocal forepaw treading, hind limb abduction, flat body posture) induced by 8-OH-DPAT (0.5 mg/kg, s.c.) were unaffected by tianeptine and 5-HTP given both singly or together. However, tianeptine significantly reduced faecal pellet formation but not cage crossings resulting from 8-OH-DPAT administration. These cage crossings but not the associated faecal pellet formation were reduced by 5-HTP. This reduction was prevented by tianeptine. The increase of extracellular 5-HT in the frontal cortex following administration of 5-HTP was opposed and the concurrent increase of extracellular 5-hydroxyindoleacetic acid (5-HIAA) was enhanced by tianeptine. The above behavioural and neurochemical findings indicate that tianeptine opposes the increase of 5-HT at receptor sites due to 5-HTP administration.
    Neuropharmacology 10/1993; 32(9):839-45. DOI:10.1016/0028-3908(93)90138-S · 4.82 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Changes in the extracellular levels of excitatory and inhibitory amino acid transmitters were studied in the rat striatum during penumbral ischaemia using intracerebral microdialysis. Effects of penumbral forebrain ischaemia were compared with those of ischaemia with sustained anoxic depolarisation and K+ (100 mM). Comparisons were also made between different groups of animals at 2 and 24 h after dialysis probe implantation. The K+ stimulus did not provoke any release of excitatory amino acids in the 24-h group, probably reflecting a decrease of functional synapses adjacent to the probe. During 30 min of penumbral ischaemia, excitatory amino acids did not reach critical concentrations in the extracellular fluid, and increases in levels of inhibitory/modulatory amino acids were similar. On the other hand, severe transient ischaemia resulted in massive synchronous release of many neuroactive excitatory and inhibitory compounds, in both the 2- and 24-h groups. These and other data suggest that changes during severe ischaemia may arise from both neurotransmitter and metabolic pools. It is concluded that ischaemic damage in the penumbra may not be related to extracellular neuroactive amino acid changes generated within this region.
    Journal of Neurochemistry 08/1993; 61(1):178-86. · 4.24 Impact Factor
  • G Curzon
    [Show abstract] [Hide abstract]
    ABSTRACT: Analyses of samples of articles in the Journal of Neurochemistry between 1956 (the year of its foundation) and 1990 were used to obtain numerical indices of the history of neurochemistry. Data suggest that the acceleration of neurochemical research did not merely reflect the increase of biochemical research in general and that it involved progressive decreases and increases of interest in major constituents and transmitters, respectively, as indicated by both numbers and citations of papers. Papers on all classes of transmitters increased steadily and in the order of amines > amino acids, acetylcholine > peptides. Within the field of brain metabolism, papers on energy metabolism decreased markedly. Use of techniques other than those of biochemistry/neurochemistry altered strikingly with decreases of histological, electrophysiological, and pharmacological methods and increases of chemical, immunological, and tissue culture methods. Citations by neuroscience core journals between 1975 and 1988 suggest that the relative prominence of neurochemistry within neuroscience has remained constant. Analyses indicate that the influence of the U.S.A. relative to that of other regions has remained fairly steady between 1956 and 1990, but that number of papers from the U.K. has declined, whereas the influences of Western Europe and other areas appear to have recently increased substantially. Sociological changes have been the virtual disappearance of single-author papers, an increase of multiauthorship (> 3), and a recent striking increase of assertive sentence titles.
    Journal of Neurochemistry 08/1993; 61(2):780-6. DOI:10.1111/j.1471-4159.1993.tb02189.x · 4.24 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Changes in the extracellular levels of excitatory and inhibitory amino acid transmitters were studied in the rat striatum during penumbral ischaemia using intracerebral microdialysis. Effects of penumbral forebrain ischaemia were compared with those of ischaemia with sustained anoxic depolarisation and K+ (100 mM). Comparisons were also made between different groups of animals at 2 and 24 h after dialysis probe implantation. The K+ stimulus did not provoke any release of excitatory amino acids in the 24-h group, probably reflecting a decrease of functional synapses adjacent to the probe. During 30 min of penumbral ischaemia, excitatory amino acids did not reach critical concentrations in the extracellular fluid, and increases in levels of inhibitory/modulatory amino acids were similar. On the other hand, severe transient ischaemia resulted in massive synchronous release of many neuroactive excitatory and inhibitory compounds, in both the 2- and 24-h groups. These and other data suggest that changes during severe ischaemia may arise from both neurotransmitter and metabolic pools. It is concluded that is- chaemic damage in the penumbra may not be related to extracellular neuroactive amino acid changes generated within this region.
    Journal of Neurochemistry 06/1993; 61(1):178 - 186. DOI:10.1111/j.1471-4159.1993.tb03553.x · 4.24 Impact Factor
  • Source
    Jun'ichi Semba, Gerald Curzon Curzon, Philip N. Patsalos
    [Show abstract] [Hide abstract]
    ABSTRACT: 1. The kinetics and metabolism of milacemide have been studied in an animal model which allows the simultaneous investigation of the temporal inter-relationships of drugs and metabolites in blood (pharmacokinetics) and cerebrospinal fluid (CSF, neuropharmacokinetics) in individual freely moving rats. 2. Milacemide dose-dependently increased CSF glycine and glycinamide (intermediary metabolite) concentrations. This confirms that milacemide is a CNS glycine prodrug. 3. Pretreatment with L-deprenyl (2 mg kg-1), a specific inhibitor of monoamine oxidase type B (MAO-B), almost completely prevented the formation of glycinamide and increased milacemide accumulation in CSF. Tmax and t1/2 were significantly increased and Cmax and AUC values were decreased for glycinamide compared to controls. Pretreatment with clorgyline (5 mg kg-1), a specific inhibitor of MAO-type A, only moderately decreased glycinamide Cmax and AUC values. 4. After milacemide administration (100, 200 and 400 mg kg-1, i.p.) serum and CSF milacemide concentrations rose linearly and dose-dependently. Serum glycinamide concentrations exhibited small dose-dependent rises but these were not linearly related. In contrast, CSF glycinamide concentrations rose linearly and dose-dependently with Cmax values 2.5, 3.2 and 4.1 times greater than the corresponding values for serum glycinamide after giving 100, 200 and 400 mg kg-1 respectively of milacemide. 5. Serum glycine concentrations were unaffected but CSF concentrations increased dose-dependently and these were significant at the higher milacemide doses (200 and 400 mg kg-1). Animals given 400 mg kg-1 milacemide had glycine values which were still significantly elevated 7 h later. 6. In conclusion, serum milacemide rapidly enters and equilibrates with the CNS compartment where it is metabolised primarily by MAO-B to glycinamide and finally to glycine. Metabolism in the peripheral compartment is negligible.
    British Journal of Pharmacology 05/1993; 108(4):1117-24. DOI:10.1111/j.1476-5381.1993.tb13514.x · 4.99 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Generalised neurotransmitter overflow into the extracellular space on cerebral ischaemia has been widely reported and implicated in events leading to subsequent neuronal death. As little is known about the effect of depth of ischaemia on these changes, we have subjected anaesthetised rats to a sequence of four challenges [high K+ stimulus, moderate (penumbral) ischaemia, severe ischaemia, cardiac arrest] and have concurrently monitored both electrophysiological parameters and changes in extracellular dopamine, serotonin, and their metabolites in the striatum. Of particular relevance to human stroke therapy was penumbral ischaemia, where ionic homeostasis was maintained even though electrical function was lost. All challenges increased extracellular monoamines, although levels were significantly greater when ischaemia was severe enough to produce sustained anoxic depolarisation. Baseline levels were rapidly restored during recovery phases. Acidic monoamine metabolites decreased significantly during each insult, returning to basal levels during reperfusion after moderate ischaemia, and to significantly higher levels after severe ischaemia. Results indicate that sustained anoxic depolarisation may be a critical factor in determining outcome after ischaemia, being associated with significantly greater release of monoamines, and impairment of electrical function recovery.
    Journal of Neurochemistry 02/1993; 60(1):128-36. DOI:10.1111/j.1471-4159.1993.tb05830.x · 4.24 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The effects of pretreatments on behavioural responses to activation of 5-HT1C receptors by m-chlorophenylpiperazine (mCPP) were investigated. The hypo locomotor and anxiogenic effects of mCPP (social interaction test) were influenced neither by previous housing (single versus grouped) nor by restraint (2 h, 24 h previously). In the absence of mCPP, 24 h group housing led to decreased social interaction and the restraint procedure led to significant decreases of feeding and locomotion. The hypophagic effect of mCPP was unaffected by previous restraint. However, chronic pretreatment with mCPP (2.5 mg/kg per day IP x 14) or with the antidepressant 5-HT reuptake inhibitor sertraline (5 mg/kg per day SC x 14) attenuated all three behaviours. The above findings are discussed with respect to published data on effects of pretreatments on responses to the activation of 5-HT1C receptors.
    Psychopharmacology 02/1993; 113(2):262-8. DOI:10.1007/BF02245708 · 3.99 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: A preliminary experiment showed that a 2.5 mg/kg dose of the 5-HT agonist 1-(3-chlorophenyl)piperazine di hydrochloride (mCPP) produced a greater reduction of food intake in female rats when weight-matched rats of both sexes were compared following 24 h food deprivation. A second experiment showed that this dose of mCPP led to higher drug concentrations in female than in male brain tissue. In two meal pattern studies non-drugged females took a shorter first meal, but ate more rapidly during that meal, than males; these differences were also seen in records of ad libitum feeding. mCPP produced an anorectic effect that lasted for < 1 h with rebound feeding becoming apparent within 1-2 h. The drug increased latency to feed, reduced the size of the first meal and feeding rate during that meal and had effects that were most marked in older rats and in female rats. In addition, effects of mCPP on water intake were as profound as those on food intake. These effects are discussed in relation to sex differences in feeding and the behavioural specificity of mCPP.
    Journal of Psychopharmacology 01/1993; 7(3):257-64. DOI:10.1177/026988119300700304 · 2.81 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: 1. The 5-HT1A ligand BMY 7378 (8-[2[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]8-azaspirol [4,5]-decane-7,9-dione dihydrochloride, 0.032-2 mg kg-1, s.c.) caused hyperphagia, a response to the activation of presynaptic 5-HT1A receptors. 2. BMY 7378 (8 mg kg-1, s.c.) and the 5-HT1A agonist (8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT), 0.10 and 0.25 mg kg-1 s.c.) also caused hypothermia. This was inhibited by (-)-pindolol (1-mg kg-1, i.p.) and not prevented by pretreatments with p-chlorophenylalanine which grossly depleted 5-hydroxytryptamine (5-HT) from terminal regions. The hypothermic effects are explicable by activation of postsynaptic 5-HT1A receptors. Infusion of BMY 7378 (8-64 micrograms) into the dorsal raphe was without convincing hypothermic effect. 3. BMY 7378 (8 mg kg-1, s.c.) inhibited another effect of activation of postsynaptic 5-HT1A receptors, i.e., the induction of components of the 5-HT syndrome by 8-OH-DPAT (0.5, 1.0 mg kg-1, s.c.) which suggests that BMY 7378 has antagonistic as well as agonistic effects at these sites. 4. Partial agonist properties of BMY 7378 at postsynaptic sites were also indicated by doses for hypothermia being much greater than those for hyperphagia i.e., ED50 (hypothermia) greater than 2 mg kg-1, ED50 (hyperphagia) = 0.010 mg kg-1. This contrasts with the similar ED50 values for both the hypothermic (ED50 = 0.08-0.10 mg kg-1) and hyperphagic (ED50 = 0.06-0.10 mg kg-1) effects of 8-OH-DPAT.5. The evidence obtained for mediation of the hypothermic response to 5-HTIA agonists by postsynaptic sites is relevant to the interpretation of the effects on it of antidepressant treatments and depressive illness.
    British Journal of Pharmacology 08/1992; 106(3):603-9. DOI:10.1111/j.1476-5381.1992.tb14382.x · 4.99 Impact Factor

Publication Stats

8k Citations
1,268.56 Total Impact Points

Institutions

  • 1975–2006
    • University of London
      Londinium, England, United Kingdom
  • 1993
    • University of Sussex
      Brighton, England, United Kingdom
  • 1986–1992
    • London Research Institute
      Londinium, England, United Kingdom
  • 1979
    • University of Kansas
      • Department of Chemistry
      Lawrence, Kansas, United States
  • 1978
    • University College Cork
      Corcaigh, Munster, Ireland
  • 1977–1978
    • The University of Manchester
      • School of Biomedicine
      Manchester, England, United Kingdom