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  • 1
    Electronic Resource
    Electronic Resource
    Behavioural, biochemical and electrophysiological studies on the motor depressant and stimulant effects of bromocriptine (1990)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 342 (1990), S. 290-299 
    Details
    ISSN: 1432-1912
    Keywords: Bromocriptine ; Dopamine autoreceptors ; Dopamine D1 receptors ; Dopamine D2 receptors ; Motor depression ; Motor stimulation ; Single cell recording ; Substantia nigra pars compacta
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Bromocriptine (BRC) produced a biphasic behavioural effect in mice; an early depressant phase which lasted for about 1 h and a later stimulant phase which lasted from about 1 to 5 h. The stimulation was blocked with SCH23390. Both phases of activity were accompanied by marked striatal DA autoreceptor effects as indicated by reductions in dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) levels and by a reduction in the accumulation of DOPA (after inhibition of nigrostriatal DA nerve firing and DOPA decarboxylase). However, while the autoreceptor effects were still evident during the behavioural stimulant phase, there was a gradual rise in DOPAC and HVA from 1 to 4 h after injection, indicating a gradually increasing DA turnover. We were unable, using a variety of behavioural and biochemical paradigms, to demonstrate any change in DA autoreceptor sensitivity after one dose of BRC. In electrophysiological studies, however, it was found that prior exposure of rats to one dose of BRC rendered them subsensitive to the rate-inhibiting effects of a second dose of BRC, as measured in anaesthetized animals using extracellular single cell recordings of identified DA neurons in the substantia nigra pars compacta. It is concluded firstly, that the stimulant phase of BRC in mice occurs despite continued occupation of the DA autoreceptors by BRC because adequate endogenous DA is available to provide the required D1 receptor stimulation and secondly, that the terminal autoreceptors in the striatum (as assessed in mice using biochemical techniques) may be regulated differently to the somatodendritic autoreceptors (as assessed electrophysiologically in rats).
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00169440
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  • 2
    Electronic Resource
    Electronic Resource
    Time course of bromocriptine induced excitation in the rat: behavioural and biochemical studies (1995)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 351 (1995), S. 146-155 
    Details
    ISSN: 1432-1912
    Keywords: Bromocriptine ; Dopamine autoreceptors ; Dopamine D1 receptors ; Dopamine D2 receptors ; Motor depression ; Motor stimulation ; Dialysis Neurotransmitter
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The aim of the present study was to further investigate the behavioural and biochemical pharmacology of the directly acting dopamine (DA) receptor agonist bromocriptine (BRC). BRC produced an initial depression of locomotion followed after about an hour by a weak but significant locomotor stimulation. The stimulation was potentiated by concomitant administration of the D1 agonist SKF38393. Ex vivo biochemical determinations indicated that reductions in dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) levels occurred in the striatum after BRC injection without a significant change in DA levels, indicating a reduced DA turnover. An increase in 5-hydroxytryptamine (5HT) and 5-hydroxyindoleacetic acid (5HIAA) levels occurred in the striatum leading to a significant increase in turnover (i.e. ratio of 5HIAA to 5HT). Noradrenaline concentrations increased in the striatum. In the cortex, sharp falls in HVA and DOPAC levels without a corresponding change in DA were observed. While there was no significant change in noradrenaline levels in this brain region, an increase in 5HIAA, but not in 5HT, levels occurred. These changes indicate an increase in 5HT turnover (ratio of 5HIAA to 5HT). In vivo dialysis indicated that extracellular levels of DA, DOPAC and HVA in the striata of freely moving rats were sharply reduced for at least 6 h after injection. In vitro binding studies showed that BRC exhibited high (Ki values in low nanomolar range) affinities for DA D2A, D2B, D3, α1 and α2 adrenergic receptors together with unexpectedly high affinity (about 1 nM) for 5HT1A receptors. The data indicate that the initial behavioural depression and later locomotor stimulation induced by BRC are accompanied by a sharp monophasic fall in striatal extracellular DA levels as indicated by dialysis studies. Since the behavioural stimulation was augmented by concomitant D1 receptor stimulation, the data suggest that the reduced DA turnover is influencing the amount of DA available to stimulate postsynaptic D1 receptors. However, the biochemical studies indicated that BRC has a high affinity for 5HT1A receptors and affects the turnover of 5HT in the brain. Thus, the behavioural effects of BRC may depend not only on effects on the DA system but also on 5HT systems.[/p]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00169328
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  • 3
    Electronic Resource
    Electronic Resource
    Bromocriptine induces marked locomotor stimulation in dopamine-depleted mice when D-1 dopamine receptors are stimulated with SKF38393 (1986)
    Springer
    Psychopharmacology 90 (1986), S. 147-149 
    Details
    ISSN: 1432-2072
    Keywords: Bromocriptine ; SKF38393 ; D-1 dopamine receptors ; D-2 dopamine receptors ; Locomotor activity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In mice pretreated with reserpine plus alphamethyl-p-tyrosine, neither the D-2 selective agonist bromocriptine, nor the D-1 selective agonist SKF38393, produced any measurable increase in locomotion in mice. However, the combination of the two agonists produced a marked and dose-dependent increase in co-ordinated locomotor activity. In mice with their dopamine stores and dopamine synthesis intact, SKF38393 was inactive by itself, but significantly enhanced the stimulant effect produced by bromocriptine. The data suggest that bromocriptine requires concomitant stimulation of D-1 receptors for the full expression of its behavioural stimulant effects.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00172888
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  • 4
    Electronic Resource
    Electronic Resource
    Further studies on the interaction between bromocriptine and SKF38393 in reserpine and alpha methyl-para-tyrosine-treated mice (1988)
    Springer
    Psychopharmacology 94 (1988), S. 321-327 
    Details
    ISSN: 1432-2072
    Keywords: Dopamine D-1 receptors ; Dopamine D-2 receptors ; Bromocriptine ; SKF38393 ; Locomotor stimulation ; Mice ; Reserpine ; Alpha methyl-p-tyrosine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In a previous report, we showed that the relatively selective dopamine (DA) D-2 agonist bromocriptine (BRC), when combined with the selective D-1 agonist SKF38393, produced in DA-depleted mice a marked locomotor stimulation, despite BRC and SKF38393 being inactive by themselves (Jackson and Hashizume 1986). The present series of experiments was designed to further explore this interaction. In all experiments, mice were pretreated with reserpine and/or alpha methyl-p-tyrosine (AMPT). In mice pretreated with reserpine, AMPT or reserpine plus AMPT, BRC plus SKF38393 produced marked excitation whether the BRC was given 3 or 1 h prior to the SKF38393 challenge. However, while there was no absolute requirement that BRC be given a certain time before SKF38393, this factor was of some importance, with the onset of locomotor stimulation produced by the combination being much more rapid if the BRC was given 3 h rather than 1 h before the SKF38393. Interestingly, the degree of locomotor stimulation produced by the combination was always greatest in the animals premedicated with reserpine alone. If AMPT was also used (with or without reserpine), the stimulation produced by the combination was reduced, which may have resulted in part from a non-specific depressant effect of the AMPT. From these results, it seems as though endogenous DA is not required for BRC to work, provided that D-1 receptors are stimulated. The BRC/SKF38393 stimulation lasted for about 4 h, but could be extended for another 3 h with a second injection of SKF38393, indicating that the biological half-life of SKF38393 is the limiting factor in the duration of stimulation produced by the combination. The stimulation produced by the combination was completely blocked by the D-1 antagonist SCH23390. The data confirm the importance of D-1 receptors for the locomotor stimulant effects of BRC.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00174683
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  • 5
    Electronic Resource
    Electronic Resource
    Bromocriptine potentiates the behavioural effects of directly and indirectly acting dopamine receptor agonists in mice (1985)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 331 (1985), S. 7-11 
    Details
    ISSN: 1432-1912
    Keywords: Bromocriptine ; Locomotor activity ; Apomorphine ; Dopamine ; receptors ; Presynaptic ; Postsynaptic ; Dopamine uptake
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary After an initial period of depression which lasted up to 90 min following injection, bromocriptine (BRC, 5–20 mg/kg, IP) produced dose-dependent and long lasting (7 h) locomotor stimulation in mice. The locomotor stimulation was antagonised by reserpine, alpha-methyl-p-tyrosine (AMPT) or haloperidol. The blockade by AMPT of BRC's locomotor stimulant effect was reversed by prior treatment of the mice with a low, behaviourally inactive dose of L-Dopa plus benserazide. In mice pretreated with reserpine, BRC enhanced the stimulant action of d-amphetamine. Moreover, in mice pretreated with reserpine plus AMPT, BRC significantly enhanced the locomotor stimulant effect of apomorphine. This ability of BRC to enhance the effect of apomorphine commenced as soon as 20 min after BRC administration and lasted for at least 8 h. The dopamine (DA) uptake inhibitor and DA receptor agonist nomifensine potentiated and prolonged the stimulant effect of BRC while inhibitor of the neuronal uptake of noradrenaline (desipramine) and 5-hydroxytryptamine (fluoxetine) were without marked effect. The results clearly show that BRC, in behavioural terms, has no efficacy per se at the postsynaptic DA receptor and that it requires either DA or the administration of an exogenous agonist such as apomorphine for the expression of its effects.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00498845
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