The stimulatory action of d-amphetamine on the respiratory centre, and its mediation by a central α-adrenergic mechanism

Mediavilla, A.; Feria, Manuel; Fernández, Jennifer Fernández; Cagigas, P.; Pazos, Ángel; Flórez, Jesús

doi:10.1016/0028-3908(79)90053-4

Cited by 15 publications

(9 citation statements)

References 23 publications

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“…Hyperthermia was not seen with administration of saline alone (Fig 1E, shown in grey). Overall, the MA-induced physiological responses in our experimental mice closely replicated characteristic MA effects in humans, including elevations in HR and MAP (Cruickshank and Dyer, 2009; Gentry et al, 2006; Mendelson et al, 2006) and an increase in RR (Jacobs and Fornal, 1997; Mediavilla et al, 1979). …”

Section: Resultssupporting

confidence: 67%

Methamphetamine causes sustained depression in cerebral blood flow

et al. 2011

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The use prevalence of the highly addictive psychostimulant methamphetamine (MA) has been steadily increasing over the past decade. MA abuse has been associated with both transient and permanent alterations in cerebral blood flow (CBF), hemorrhage, cerebrovascular accidents and death. To understand MA-induced changes in CBF, we exposed C56BL/6 mice to an acute bolus of MA (5 mg/kg MA, delivered IP). This elicited a biphasic CBF response, characterized by an initial transient increase (~5 min) followed by a prolonged decrease (~30 min) of approximately 25% relative to baseline CBF -as measured by laser Doppler flowmetry over the somatosensory cortex. To assess if this was due to catecholamine derived vasoconstriction, phentolamine, an α-adrenergic antagonist was administered prior to MA treatment. This reduced the initial increase in CBF but failed to prevent the subsequent, sustained decrease in CBF. Consistent with prior reports, MA caused a transient increase in mean arterial blood pressure, body temperature and respiratory rate. Elevated respiratory rate resulted in hypocapnia. When respiratory rate was Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access

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Section: Resultssupporting

confidence: 67%

Methamphetamine causes sustained depression in cerebral blood flow

et al. 2011

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“…The results of the present in vitro experiments agree with these previous results. On the other hand, there seems to be no general agreement on the effects of NA (Bolme & Fuxe, 1973;Mediavilla et al, 1979), dopamine (Bolme et al, 1977;Hedner et al, 1982) and 5-HT (Feldberg & Sherwood, 1954;Lundberg et al, 1980) Such disagreement can be ascribed to variable anaesthetic conditions, to species differences among experimental animals, or to possible effects of the drugs on the peripheral organs. In our isolated CNS preparation, the indirect action ofdrugs on respiration through peripheral organs was completely excluded, enabling us to study the direct effect of drugs on the respiratory centre in the brainstem in an anaestheticfree environment.…”

Section: Discussionmentioning

confidence: 99%

“…The results of the present in vitro experiments agree with these previous results. On the other hand, there seems to be no general agreement on the effects of NA (Bolme & Fuxe, 1973;Mediavilla et al, 1979), dopamine (Bolme et al, 1977;Hedner et al, 1982) and 5-HT (Feldberg & Sherwood, 1954;Lundberg et al, 1980) in whole animal experiments. For instance, Bolme & Fuxe (1973) Such disagreement can be ascribed to variable anaesthetic conditions, to species differences among experimental animals, or to possible effects of the drugs on the peripheral organs.…”

Section: Discussionmentioning

confidence: 99%

A pharmacological study on respiratory rhythm in the isolated brainstem‐spinal cord preparation of the newborn rat

Murakoshi

Suzue

Tamai

1985

British J Pharmacology

181

111

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1 An in vitro brainstem-spinal cord preparation of the newborn rat was used to examine the effects of neurotransmitters and transmitter candidates on respiratory frequency. 2 Spontaneous periodic depolarization of the spinal ventral roots of the 4th or 5th cervical segment was observed at a frequency of 5-15 min-' constantly for more than 5 h. The frequency of this depolarization was monitored as an index of the respiratory frequency. 3 An elevation of the concentration of Ca2+ or Mg2+ caused a decrease in the respiratory frequency, whereas an elevation of K+ concentration caused an increase. The frequency was also increased by a reduction of pH. The highest frequency was observed at 27-280C. 4 Dopamine, 5-hydroxytryptamine, histamine, acetylcholine, glutamic acid, substance P, and thyrotropin releasing hormone accelerated the respiratory frequency when applied by perfusion to the brainstem, whereas noradrenaline, y-aminobutyric acid, glycine, and [Met5] enkephalin and [Leu5] enkephalin slowed the frequency. Experiments with antagonists suggested that the stimulant effect of acetylcholine on respiratory frequency was mediated mainly by muscarinic receptors and the depressant effect of noradrenaline was mediated by a-adrenoceptors.

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“…Additionally, arterial blood CO 2 concentration changed less than it did in our saline-treated rats during the scanning period, which would indicate that hypo/hypercapnia had not occurred. D-Amphetamine caused a dose-dependent increase in respiratory rate in anaesthetised rats, and brain regions involved in this effect include the rostral pontine structures in the region of the medial parabrachial nuclei and the reticular respiratory oscillator (Mediavilla et al 1979). As the L-isomer is more effective at promoting the availability of noradrenaline at postsynaptic receptors, this may enhance the inspiratory 'off-switch' within pontine structures.…”

Section: Effects Of the Isomers On Respiratory Ratementioning

confidence: 99%

Differential effects of the d- and l- isomers of amphetamine on pharmacological MRI BOLD contrast in the rat

et al. 2007

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Rationale The D-and L-amphetamine sulphate isomers are used in the formulation of Adderall XR®, which is effective in the treatment of attention-deficit hyperactivity disorder (ADHD). The effects of these isomers on brain activity has not been examined using neuroimaging. Objectives This study determines the pharmacological magnetic resonance imaging blood-oxygenation-level-dependent (BOLD) response in rat brain regions after administration of each isomer. Materials and methods Rats were individually placed into a 2.35 T Bruker magnet for 60 min to achieve basal recording of variation in signal intensity. Either saline (n=9), D-amphetamine sulphate (2 mg/kg, i.p.; n=9) or L-amphetamine sulphate (4 mg/kg, i.p.; n=9) were administered, and recording continued for a further 90 min. Data were analysed for BOLD effects using statistical parametric maps. Blood pressure, blood gases and respiratory rate were monitored during scanning. Results The isomers show overlapping effects on the BOLD responses in areas including nucleus accumbens, medial entorhinal cortex, colliculi, field CA1 of hippocampus and thalamic nuclei. The L-isomer produced greater global changes in the positive BOLD response than the D-isomer, including the somatosensory and motor cortices and frontal brain regions such as the orbitofrontal cortices, prelimbic and infralimbic cortex which were not observed with the D-isomer. ConclusionsThe amphetamine isomers produce different BOLD responses in brain areas related to cognition, pleasure, pain processing and motor control probably because of variations on brain amine systems such as dopamine and noradrenaline. The isomers may, therefore, have distinct actions on brain regions affected in ADHD patients.

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The stimulatory action of d-amphetamine on the respiratory centre, and its mediation by a central α-adrenergic mechanism

Cited by 15 publications

References 23 publications

Methamphetamine causes sustained depression in cerebral blood flow

Methamphetamine causes sustained depression in cerebral blood flow

A pharmacological study on respiratory rhythm in the isolated brainstem‐spinal cord preparation of the newborn rat

Differential effects of the d- and l- isomers of amphetamine on pharmacological MRI BOLD contrast in the rat

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