Effects of Respiratory Stimulants on Cerebral Metabolism and Blood Flow

Nehlig, Astrid

doi:10.1159/000244062

Cited by 5 publications

(4 citation statements)

References 23 publications

(28 reference statements)

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“…It has been shown that caffeine, in addition to dopamine, also increases the turnover of other monoaminergic neurotransmitters such as serotonin and noradrenalin (Fredholm et al, 1999) which may play different roles in alcohol and nicotine addiction. Also, effects of caffeine on cerebral glucose utilization (Nehlig, 1986), its central vasoconstrictive effect (Nehlig, 1994) and its other, as yet unknown, actions may contribute to its effect on alcohol and nicotine intake. In conclusion, these preclinical studies with caffeine suggest that adenosine receptor systems in the brain may play an important role in both alcohol and nicotine intake and deserve further preclinical and clinical studies regarding these and other addictions.…”

Section: Discussionmentioning

confidence: 99%

Effects of Caffeine on Alcohol Consumption and Nicotine Self-Administration in Rats

Rezvani

Sexton

Johnson

et al. 2013

Alcohol Clin Exp Res

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Background Caffeine, alcohol and nicotine are three of the most widespread self-administered psychoactive substances, which are known to be extensively co-administered. However, little is known about the degree to which they may mutually potentiate each other’s consumption. Methods In the current set of studies, we examined in rats the effect of caffeine administration on alcohol drinking and intravenous (i.v.) self-administration of nicotine. In male alcohol-preferring P rats, caffeine (5, 10 and 20 mg/kg) or the saline vehicle was administered acutely either by subcutaneous (S.C.) injection or orally (PO) by gavage. In a chronic study, the effect of oral caffeine (5 and 20 mg/kg) on alcohol intake over a 10-day period was tested. In another experiment, the effect of acute oral administration of caffeine (20 mg/kg) or saline on saccharin intake (0.2% solution) was determined in P rats. Effects of 20 mg/kg caffeine on motor activity were also determined in P rats. Finally, the effects of acute oral caffeine administration on nicotine self-administration in Sprague-Dawley rats were also determined. Results Both routes of administration of caffeine, S.C. and PO, caused a significant dose-related decrease in alcohol intake and preference during free access to alcohol and after 4-day deprivation of alcohol. However, the low dose of 5 mg/kg caffeine increased alcohol intake. Acute oral caffeine also reduced saccharin intake. Acute systemic administration of 20 mg/kg caffeine did not exert a significant effect on motor activity. In Sprague-Dawley rats trained to self-administer i.v. nicotine, acute oral administration of caffeine significantly increased self-administration of nicotine in a dose-related manner. Conclusions These results suggest that adenosine receptor systems may play a role in both alcohol and nicotine intake and deserve further study regarding these addictions.

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Section: Discussionmentioning

confidence: 99%

Effects of Caffeine on Alcohol Consumption and Nicotine Self-Administration in Rats

Rezvani

Sexton

Johnson

et al. 2013

Alcohol Clin Exp Res

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“…1,250 g is associated with the total dosage and duration of doxapram therapy. However, doxapram is generally considered a drug with a good margin of safety and is widely used in preterm infants [14] . …”

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confidence: 99%

Brain Hemodynamic Effects of Doxapram in Preterm Infants

Dani¹,

Bertini²,

Pezzati³

et al. 2006

Neonatology

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Background: Doxapram is a respiratory stimulant widely used for the treatment of idiopathic apnea of prematurity, although it has been demonstrated that it can induce a transient decrease of cerebral blood flow and that isolated mental delay in infants weighing <1,250 g is associated with the total dosage and duration of doxapram therapy. Objectives: To evaluate the effects of doxapram on cerebral hemodynamics in preterm infants using cerebral Doppler ultrasonography and near-infrared spectroscopy. Methods: Preterm infants who required treatment with doxapram for apnea of prematurity unresponsive to caffeine were treated with doxapram at an hourly dose of 0.5 mg·kg^–1·h^–1, followed by 1.5 and 2.5 mg·kg^–1·h^–1. Results: 20 preterm infants were studied. Doxapram induced a significant decrease of oxygenated hemoglobin (O₂Hb) and cerebral intravascular oxygenation (HbD = O₂Hb – HHb) and an increase of HHb and CtOx concentrations, while cerebral blood volume and cerebral blood flow velocity did not change. Conclusions: Doxapram infusion induces the increase of cerebral oxygen consumption and requirement and the contemporary decrease of oxygen delivery probably mediated by a decrease of cerebral blood flow. Caution must be recommended in prescribing this drug for apnea of prematurity.

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“…It is therefore possible that the cerebrovascular resistance is slightly higher in nonexperimental settings. However, a counteracting effect of doxapram is possible as mild cerebral vasoconstriction has been reported after its use (27)(28)(29).…”

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confidence: 99%

Cerebral Pressure Autoregulation and Vasoreactivity in the Newborn Rat

et al. 2005

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Perinatal brain injury has been associated with impaired cerebral blood flow (CBF) pressure autoregulation. The brain of 3-to 5-d-old rat pups is immature and similar to that of a preterm infant, and therefore we tested cerebral vasoreactivity in that animal. CBF pressure autoregulation was tested in 20 Wistar pups during normocapnia and hypercapnia, respectively. Hypotension was induced by hemorrhage and cerebral perfusion was monitored with laser Doppler flowmetry and near-infrared spectroscopy. Systolic blood pressure was measured noninvasively from the tail. During normocapnia, the autoregulatory plateau was narrow. Resting systolic blood pressure (SBP) was 39.2 mm Hg and CBF remained constant until SBP decreased below 36.0 mm Hg (SE 0.8). Below the lower limit, CBF declined by a mean of 2.7% per mm Hg [95% confidence interval (CI), 2.4 -3.0%], and hemoglobin difference (HbD) and total hemoglobin (HbT) changed proportionally to CBF. After inhalation of carbon dioxide, CBF increased significantly by a mean of 17.7% (95% CI, 13.7-22.8%). The CBF-CO 2 reactivity was estimated to 13.4% per kPa (95% CI, 2-24.8%), p ϭ 0.026. Over the range of SBP (6 -54 mm Hg), a linear relationship between CBF and SBP was found during hypercapnia, indicating abolished pressure autoregulation. A linear correlation between CBF and HbD was found (r ϭ 0.80). CBF pressure autoregulation and reactivity to CO 2 operate in the newborn rat. This model may be useful for future investigations concerning perinatal pathophysiology in the immature brain. In very preterm infants, brain injury has been associated with impaired pressure autoregulation of CBF. Accordingly, periventricular hemorrhage may result from abrupt hyperperfusion whereas periventricular leukomalacia has been related to ischemia (1-9).Cerebral pressure autoregulation refers to vascular mechanisms whereby CBF is held within constant levels during variations in perfusion pressure. Perfusion is thus maintained over a range of pressures by appropriate alterations in the diameter of precapillary arterioles. However, the lower limit of autoregulation is reached when the vessels become fully dilated and, beyond that point, any further decrease in pressure results in proportional drops in CBF. Several conditions may affect the autoregulatory plateau and increased CBF as well as complete pressure passiveness secondary to vasodilatation is observed during hypercapnia, hypoglycaemia, hypoxia, and seizure (10 -13).Cerebral pressure autoregulation has been documented in several newborn animals such as piglets, lambs, and puppies (14 -19). Most of these animals have rather mature brains at birth, and to compare vascular physiology with that of a preterm infant, the newborn rat pup served as a model (20,21). Because we could not control ventilation in this immature animal, we evaluated the cerebrovascular response to hemorrhagic hypotension during normocapnia and carbon dioxide inhalation. The hypothesis was that pressure autoregulation operates normally in the healthy immature brain. METH...

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Effects of Respiratory Stimulants on Cerebral Metabolism and Blood Flow

Cited by 5 publications

References 23 publications

Effects of Caffeine on Alcohol Consumption and Nicotine Self-Administration in Rats

Effects of Caffeine on Alcohol Consumption and Nicotine Self-Administration in Rats

Brain Hemodynamic Effects of Doxapram in Preterm Infants

Cerebral Pressure Autoregulation and Vasoreactivity in the Newborn Rat

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