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  • 1
    Electronic Resource
    Electronic Resource
    In Vivo Evidence that Lithium Inactivates Gi Modulation of Adenylate Cyclase in Brain (1992)
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 59 (1992), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: In vivo microdialysis of cyclic AMP from prefron-tal cortex complemented by ex vivo measures was used to investigate the possibility that lithium produces functional changes in G proteins that could account for its effects on adenylate cyclase activity. Four weeks of lithium administration (serum lithium concentration of 0.85 ±0.05 mM; n= 11) significantly increased the basal cyclic AMP content in dialysate from prefrontal cortex of anesthetized rats. Forskolin infused through the probe increased dialysate cyclic AMP, but the magnitude of this increase was unaffected by chronic lithium administration. Inactivation of the inhibitory guanine nucleotide binding protein Gi with pertussis toxin increased dialysate cyclic AMP in control rats, as did stimulation with cholera toxin (which activates the stimulatory guanine nucleotide binding protein Gs). The effect of pertussis toxin was abolished following chronic lithium, whereas the increase in cyclic AMP after cholera toxin was enhanced. In vitro pertussis toxin-catalyzed ADP ribosyla-tion of αi (and αo) was increased by 20% in prefrontal cortex from lithium-treated rats, but the αi and αs contents (as determined by immunoblot) as well as the cholera toxin-catalyzed ADP ribosylation of αs were unchanged. Taken together, these results suggest that chronic lithium administration may interfere with the dissociation of Gi into its active components and thereby remove a tonic inhibitory influence on adenylate cyclase, with resultant enhanced basal and cholera toxin-stimulated adenylate cyclase activity.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1471-4159.1992.tb08891.x
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  • 2
    Electronic Resource
    Electronic Resource
    Quantitative Examination of Tissue Concentration Profiles Associated with Microdialysis (1992)
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 58 (1992), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Spatial solute concentration profiles resulting from in vivo microdialysis were measured in rat caudate-putamen by quantitative autoradiography. Radiolabeled sucrose was included in the dialysate, and the tissue concentration profile measured after infusions of 14 min and 61.5 min in an acute preparation. In addition, the changes in sucrose extraction fraction over time were followed in vivo and in a simple in vitro system consisting of 0.5% agarose. These experimental results were then compared with mathematical simulations of microdialysis in vitro and in vivo. Simulations of in vitro microdialysis agreed well with experimental results. In vivo, the autoradiograms of the tissue concentration profiles showed clear evidence of substantial differences between 14 and 61.5 min, even though the change in extraction fraction was relatively small over that period. Comparison with simulated results showed that the model substantially underpre-dicted the observed extraction fraction and overall amount of sucrose in the tissue. A sensitivity analysis of the various model parameters suggested a tissue extracellular volume fraction of approximately 40% following probe implantation. We conclude that the injury from probe insertion initially causes disruption of the blood-brain barrier in the vicinity of the probe, and this disruption leads to an influx of water and plasma constituents, causing a vasogenic edema.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1471-4159.1992.tb09346.x
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  • 3
    Electronic Resource
    Electronic Resource
    Quantitative Microdialysis: Analysis of Transients and Application to Pharmacokinetics in Brain (1991)
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 57 (1991), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: The behavior of a microdialysis probe in vivo is mathematically described. A diffusion-reaction model is developed that not only accounts for transport of substances through tissues and probe membranes but also accounts for transport across the microvasculature and metabolism. Time-dependent equations are presented both for the effluent microdialysate concentration and for concentration profiles about the probe. The analysis applies either to measuring the tissue pharmacokinetics of drugs administered systemically, or for sampling of endogenously produced substances from tissue. In addition, an expression is developed for the transient concentration about the probe when it is used as an infusion device. All mathematical expressions are found to be a sum of an algebraic and an integral term. Theoretical prediction of time-dependent probe behavior in brain has been compared with experimental data for acetaminophen administered at 15 mg/kg to rats by intravenous bolus. Plasma and whole striatal tissue samples were used to describe plasma kinetics and to estimate a capillary permeability-area product of 0.07 min-1. Theoretical prediction of transient effluent dialysate concentrations exhibited close agreement with experimental data over 60 min. Terminal decline of the dialysate effluent concentration was slightly overestimated but theoretical concentrations still lay within the 95% confidence interval of the experimental data at 112 min. Microvasculature transport and metabolism play major roles in determining microdialysate transient responses. Extraction fraction (recovery) has been shown to be a declining function in time for five probe operating conditions. High rates of metabolism and/or capillary transport affect the time required to approach steady-state extraction, shortening the time as the rates increase. Conversely, for substances characterized by low permeabilities and negligible metabolism, experimental situations exist that are predicted to have very slow approaches to microdialysis steady state.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1471-4159.1991.tb02105.x
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  • 4
    Electronic Resource
    Electronic Resource
    Effects of Different Semipermeable Membranes on In Vitro and In Vivo Performance of Microdialysis Probes (1990)
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 54 (1990), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The in vitro and in vivo performance of three different semipermeable microdialysis membranes was compared: a proprietary polycarbonate-ether membrane made by Carnegie Medecin; cuprophan, a regenerated cellulose membrane; and polyacrylonitrile. When microdialysis probes were tested in a stirred in vitro solution, large and statistically significant differences among the three membranes in extraction of acid metabolites (3,4-dihydroxyphenylacetic acid, 5-hydroxyindoleacetic acid, and homovanillic acid) and acetaminophen were found. Polyacrylonitrile had the highest extractions in vitro. In contrast, when microdialysis probes were implanted in vivo (in rat striatum), extraction of acid metabolites and acetaminophen did not differ significantly among the different membranes. These results are consistent with predictions made by a mathematical model of microdialysis and can be explained by the fact that in vitro the main factor limiting extraction is membrane resistance to diffusion, whereas tissue resistance to diffusion plays a more dominant role in vivo. These findings suggest that (aside from differences in surface area), the choice of semipermeable membrane will generally have little effect on in vivo microdialysis results. Furthermore, in vitro measurements of microdialysis probe extractions are not a reliable way of calibrating in vivo performance.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1471-4159.1990.tb01982.x
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  • 5
    Electronic Resource
    Electronic Resource
    Intravenous alprazolam challenge in normal subjects (1989)
    Springer
    Psychopharmacology 99 (1989), S. 508-514 
    Details
    ISSN: 1432-2072
    Keywords: Alprazolam ; Catecholamines ; Blood pressure ; Neuroendocrine challenge
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Alprazolam, a novel benzodiazepine derivative is thought to be effective in the treatment of anxiety, panic, and depressive disorders. There is considerable interest in alprazolam's mechanism of action, particularly whether its profile of actions might resemble that of the α2 adrenore-ceptor agonist, clonidine. The present study assessed the biochemical, cardiovascular, and behavioral responses of healthy volunteers to acute intravenous infusions of alprazolam and placebo. Alprazolam reduced ACTH and cortisol while increasing growth hormone. There was a transient reduction in plasma norepinephrine and only modest effects on cardiovascular parameters. Subjects became quite sedated after intravenous alprazolam. This pharmacodynamic profile resembles that previously reported for traditional benzodiazepines, although alprazolam may be a more potent stimulator of growth hormone release. Alprazolam's effects on growth hormone resemble those of clonidine, but unlike clonidine, alprazolam has relatively little effect on plasma catecholamine and cardiovascular parameters. This suggests that α2 mechanisms do not play a primary role in alprazolam's mode of action. Since alprazolam infusion affects three different measures (ACTH/cortisol, growth hormone, and plasma norepinephrine) thought to be dysregulated in depression, challenge with intravenous alprazolam may prove to be a useful “probe” in affective disorders.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00589900
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  • 6
    Electronic Resource
    Electronic Resource
    Dose-dependent effects of intravenous alprazolam on neuroendocrine, biochemical, cardiovascular, and behavioral parameters in humans (1993)
    Springer
    Psychopharmacology 111 (1993), S. 295-300 
    Details
    ISSN: 1432-2072
    Keywords: Alprazolam ; Neuroendocrine parameters ; Cardiovascular parameters ; Biochemical parameters ; Behavioral parameters
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Neuroendocrine, biochemical, cardiovascular, and behavioral parameters were assessed in seven normal volunteers for 2 h after intravenous administration of alprazolam (APZ). Three doses of APZ (0.003, 0.007, and 0.02 mg/kg) were administered to each subject in a random order with at least 4 days between infusions. Plasma growth hormone and sedation increased in a dose dependent manner after APZ, and there was a dose dependent change in the shape of the cortisol response to APZ. No dose-response relationships were evident for plasma ACTH and norepinephrine. These differences in dose-response relationships may reflect the involvement of multiple systems in controlling neuroendocrine, biochemical, and subjective responses to APZ infusion. The optimal dose of APZ needed to produce a neuroendocrine or behavioral change appears to differ depending on the parameter of interest.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02244944
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  • 7
    Electronic Resource
    Electronic Resource
    Clinical investigation of monoamine neurotransmitter interactions (1993)
    Springer
    Psychopharmacology 112 (1993), S. S76 
    Details
    ISSN: 1432-2072
    Keywords: Monoamine neurotransmitter systems ; Schizophrenia ; Clozapine ; Neuroleptics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Monoamine neurotransmitter systems are widely thought to be involved in the pathophysiology of affective disorders and schizophrenia and the mechanism of action of antidepressant and antipsychotic drugs. Previous clinical studies have focused on individual monoamine function in isolation, even though a large number of preclinical studies have demonstrated that monoamine neurotransmitter systems interact with one another. In the present paper, preclinical data on monoamine neurotransmitter interactions are reviewed, and two methods for examining monoamine neurotransmitter system interactions in clinical data are presented. One of the best replicated findings in biological psychiatry is that monoamine metabolites in CSF correlate with one another. The degree of correlation may be in part a measure of the degree of interaction between the parent monoamine neurotransmitter systems. Another approach to studying interactions is the use of HVA/5HIAA and HVA/MHPG ratios as an index of interactions between 5HT-DA and NE-DA. When these methods are applied in schizophrenia, patients are found to have decreased monoamine metabolite correlations compared to normal controls. Metabolite correlations increase significantly after antipsychotic treatment, and the HVA/5HIAA and HVA/MHPG ratios also increase, suggesting that neuroleptics may act in part by strengthening interactions between monoamines. BPRS ratings are negatively correlated with HVA/5HIAA and HVA/MHPG so that patients with higher ratios have fewer symptoms, particularly after treatment. These results provide direct experimental support for hypotheses suggesting that interactions between monoamine neurotransmitters are important in schizophrenia. Some of the effects of the atypical neuroleptic, clozapine, on metabolite correlations and ratios are also discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02245010
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  • 8
    Electronic Resource
    Electronic Resource
    Activation in young rats induced by LY134046, an inhibitor of phenylethanolamine N-methyltransferase (1989)
    Springer
    Psychopharmacology 98 (1989), S. 240-244 
    Details
    ISSN: 1432-2072
    Keywords: Phenylethanolamine N-methyltransferase ; Epinephrine ; Locomotor activity ; Development
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract LY134046, a potent, selective inhibitor of rat brain phenylethanolamine N-methyltransferase, was shown to increase activity in 18- and 19-day-old rats. The effects on day 25 were different, with LY134046 causing a decrease in activity. The effects of yohimbine, a selective antagonist of the alpha-2 adrenergic receptor, were markedly different from LY134046, causing a decrease in activity on day 19. These data suggest that epinephrine synthesis may play an inhibitory role in the regulation of activity in young rats.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00444698
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