Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Caffeine”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 973 records · Page 54Linked to original sources
PubMed1994

Enhancement of CDDP cytotoxicity by caffeine is characterized by apoptotic cell death.

The ability of caffeine, an agent that suppresses cell replication by inhibiting deoxyribonucleic acids (DNA) repair, to modulate the cytotoxicity of cis-diamminedichloroplatinum (CDDP) was investigated in murine lymphoma cell line EL-4. EL-4 cells were precultured with or without 20 micrograms/ml CDDP for 1 h and then cultured in the presence of 5 mM caffeine up to 48 h after reseeding. In CDDP-pretreated cells, suppression of cell growth and decrease in cell viability from 24 h were observed. Cell cycle arrest in G2 + M phase and a concomitant increase in both rhodamine 123 (R123) uptake and cell size (forward scatter) were observed in these cells. Treatment with caffeine alone suppressed growth rate, R123 uptake, cell size, and frequency of S phase fraction in the cell cycle. Combination of the two agents, CDDP+caffeine, strongly suppressed not only cell viability but also R123 uptake and cell size, compared with CDDP pretreatment alone. DNA histogram analysis by flow cytometry revealed that cultivation with caffeine hastened G2 + M arrest in CDDP-pretreated cells by reduction in the time of passing through S phase. DNA fragmentation was observed following incubation of CDDP-pretreated cells with caffeine for 16 h when marked accumulation in G2 + M phase was observed. The intensity of these ladder fragments increased in a time-related manner. These results demonstrate that enhancement of cytotoxic activity against CDDP-treated cells by caffeine is characterized by an acceleration of DNA degradation in G2 + M phase, namely apoptotic cell death. The fact that induction of DNA fragmentation during G2 + M phase by caffeine modulates the cytotoxicity of CDDP may give rise to a new combination regime of chemotherapy against malignant tumor cells.

Animals↗
PubMed1997

Modulation in cell cycle and cyclin B1 expression in irradiated HeLa cells and normal human skin fibroblasts treated with staurosporine and caffeine.

The comparative effects of staurosporine or caffeine on G2-phase arrest and cyclin B1 expression in human skin fibroblasts (HSF) and transformed HeLa cells following gamma-irradiation were examined by flow cytometry. Contrary to some earlier reports with HeLa cells, the arrest in G2 after irradiation was accompanied by an increase in cyclin B1 levels in both asynchronous and synchronized HeLa cells irradiated in early S phase. Caffeine and staurosporine were equally effective in attenuating both the radiation-induced increase in cyclin B1 expression and the prolongation of G2 in synchronous and asynchronous HeLa cell populations. Staurosporine treatment was less effective in down-regulating cyclin B1 expression in asynchronous HeLa cells at earlier time points following irradiation when compared to caffeine-treated cells. In synchronized HeLa cells, down-regulation of an irradiation-induced increase in cyclin B1 expression was similar to either staurosporine or caffeine treatments, with caffeine being more effective at later time points. An increase in cyclin B1 expression was also observed in irradiated HSF cells (synchronous and asynchronous), which decreased when the cells were treated with staurosporine or caffeine. However, staurosporine was ineffective in attenuating the radiation-induced prolongation of G2 in synchronous and asynchronous HSF cells, whereas treatment of irradiated synchronous or asynchronous HSF cells with caffeine significantly reduced the prolongation of G2. These results suggest that both staurosporine and caffeine treatments act on different pathways of cell cycle control in normal and transformed cells, in terms of attenuation of G2 block and diminution of elevated levels of cyclin B1 expression, in response to radiation.

Amino Acid Sequence↗
PubMed1994

Coteratogenic effects of caffeine.

Coteratogenicity studies have been carried out using various physical and chemical agents along with caffeine. For ionizing radiation in mice, enhancement of teratogenic responses (cleft palate, limb malformations) was noted with single systemic bolus doses of 50 to 200 mg/kg. Studies in rats with ethanol or nicotine reveal only an additive effect with caffeine. There are mixed results with chemical carcinogens and caffeine with some studies showing enhancement and others showing that caffeine inhibits the teratogenic effect of some carcinogens. The time of treatment, at the time of carcinogen exposure for the inhibition and later in the gestation period for the enhancement, appears to be the critical factor. For a variety of pharmaceutical agents (acetazolamide, mitomycin C, hydroxyurea, 5-fluorouracil), caffeine was shown to enhance the teratogenic effect of the agent. With 5-azacytidine in rats, caffeine suppressed limb malformations. Administration of inhibitors of beta-adrenergic function reduces the teratogenic effect of caffeine in mice. The interpretation of the experimental studies in terms of human hazard is complicated by the general use of high-dose bolus exposures which are not typical of human exposures, and the use of test systems that are not readily applicable to humans. The studies in human populations show clearly that caffeine itself has no link to negative birth outcome, and in the few instances where it has been examined there appears to be no interaction between coffee consumption and either alcohol consumption or smoking on pregnancy outcome.

Animals↗
PubMed1982

The effect of pregnancy on the pharmacokinetics of caffeine.

Caffeine is eliminated mainly by metabolism to demethylated and oxidised derivatives. High individual variability is therefore expected from variations and changes in the capability of the organism to metabolize xenobiotics. An increase of the half-life of elimination of caffeine has been reported during the final weeks of pregnancy. In this study, the half-lifes of caffeine were determined by HPLC-analysis of samples of saliva in male and non-pregnant females and in women during pregnancy and after parturition. The half-life of caffeine increases from an average of 3 h for non-pregnant women to 10.5 h during the last 4 weeks of pregnancy. This increase is already occurring during the first part of pregnancy. The individual values could not be correlated with age, weight, consumption of coffee or smoking habits. An increase of the apparent volume of distribution can also be ruled out as an explanation for the marked increase of the half-life. The main effect of a prolonged half-life is the accumulation of caffeine in the body, unless the consumption is reduced appropriately. Thus, the greatly increased half-life of caffeine during pregnancy could produce adverse effects at a consumption which although considered as high is not excessive under normal conditions. This possibly explains the observation that heavy coffee drinking during pregnancy is linked to a low birthweight in the neonate. Due to the non-specificity of some of the symptoms of caffeine toxicity, pregnant women with such symptoms might be unable to trace the reason for their discomfort if they are not instructed by their physician about the higher susceptibility to caffeine during pregnancy.

Caffeine↗
PubMed1988

Reversal by caffeine of triazolam-induced impairment of waking function.

Twelve, healthy normal men aged 21-25 years received each of four treatments (triazolam placebo plus caffeine placebo, triazolam 0.50 mg plus caffeine placebo, triazolam 0.50 mg plus caffeine 4 mg/kg, triazolam 0.50 mg plus caffeine 8 mg/kg), double blind, in a Latin-Square design. Triazolam or placebo was administered at 0830 and caffeine or placebo at 1000 and 1245. On two memory tasks, administered at 1015 with an immediate recall and a delayed recall at 1230 following a 90 min nap (1030-1200), both immediate and delayed recall was impaired by triazolam. Neither caffeine dose reversed the impairments. Sleep latency and sleep efficiency were improved by triazolam and not reversed by caffeine. On a performance battery presented at 1300 most measures of performance were impaired by triazolam; in general the caffeine dose of 4 mg/kg partially reversed the effect while the dose of 8 mg/kg completely restored performance.

Adult↗
PubMed1994

Caffeine inhibits cytoplasmic Ca2+ oscillations induced by carbachol and guanosine 5'-O-(3-thiotriphosphate) in hyperpolarized pancreatic beta-cells.

The effects of caffeine on cytoplasmic Ca2+ oscillations induced by carbachol and guanosine 5'-O-(3-thiotriphosphate) (GTP-gamma-S) were studied in individual mouse pancreatic beta-cells clamped at a hyperpolarized potential. Addition of 10 mM caffeine did not affect the cytoplasmic Ca2+ concentration ([Ca2+]i) in beta-cells exposed to 20 mM glucose and hyperpolarized with diazoxide. Under similar conditions 100 microM carbachol induced a typical response with a marked [Ca2+]i peak followed by a lower sustained elevation. Irrespective of whether 10 mM caffeine was present, there were [Ca2+]i transients with frequencies of 1-5/min superimposed on the sustained phase in 50-60% of the cells. In previously non-exposed cells the introduction of 10 mM caffeine caused temporary lowering of the sustained phase with disappearance of the transients. Subsequent omission of caffeine in the continued presence of carbachol caused a marked [Ca2+]i peak followed by reappearance of the [Ca2+]i transients. However, in cells oscillating in the presence of caffeine its omission caused disappearance of the transients. In this case reintroduction of caffeine restored the transients. In cells kept at -70 mV by a patch pipette containing 100 microM GTP-gamma-S and 3 mM Mg-ATP there were [Ca2+]i transients with frequencies of 0.5-2.5/min. These transients were sufficiently pronounced to activate repetitively a K+ current. Addition of 10 mM caffeine caused disappearance of the [Ca2+]i transients or reduction of their amplitudes and frequencies.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1993

Influence of usual intake of dietary caffeine on single-dose kinetics of theophylline in healthy human subjects.

The influence of usual multiple ingestions of dietary caffeine on oral single-dose pharmacokinetics of theophylline has been investigated in 6 healthy male subjects. The subjects consumed 2 to 7 cups of regular instant coffee during the 24 h study period. Their mean serum concentrations of caffeine varied from 1.2 to 3.1 mg/l. After their usual intake of dietary caffeine, the serum concentrations of theophylline from 3 to 24 h after administration were significantly higher than after deprivation of dietary caffeine. The apparent elimination of theophylline half-life was prolonged from 6.3 (0.61) h (mean with (SEM)) to 8.3 (0.47) h (32% increase, P < 0.01) and the total body clearance was reduced from 55.0 (1.31) ml.h-1.kg-1 to 42.5 (2.63) ml.h-1.kg-1 (23% decrease, P < 0.001). Saturation of theophylline metabolism and/or competition between theophylline and caffeine metabolism in addition to theophylline derived from caffeine may be the cause of the delayed elimination of theophylline. The present study has indicated that a significant reduction in theophylline metabolism may be caused by a conventional intake of dietary caffeine. In bronchodilator therapy with theophylline, therefore, the daily consumption of caffeine should be taken into consideration.

Administration, Oral↗
PubMed1991

Effects of caffeine with repeated dosing.

We have recently demonstrated dose-dependency of caffeine metabolism under multiple dosing conditions. Whether there are persistent pharmacodynamic actions of caffeine under such circumstances is the focus of this report. Nine healthy subjects were given, in randomized 5 day blocks, placebo, 4.2 (low) and 12 (high) mg.kg-1.day-1 of caffeine in 6 divided doses. After 5 days, complete tolerance developed to the effects of caffeine on blood pressure, heart rate and plasma glucose concentrations. The 24-h area under the curve (AUC) for plasma norepinephrine and the AUC for the total sum of free fatty acids (FFA) both demonstrated a trend to increase with the high dose caffeine treatment. When the AUC for norepinephrine was split into 12 h time periods, a significant difference between the placebo and the high dose treatment block was seen. We conclude that regular consumption of 12 mg.kg-1 of caffeine per day (equivalent to approximately 6 to 11 cups of coffee per day) may produce pharmacodynamic effects not completely compensated for by the development of tolerance. Mechanisms of tolerance may be overwhelmed by the nonlinear accumulation of caffeine and other methylxanthines in the body when caffeine metabolism becomes saturable.

Adult↗
PubMed1992

Influence of caffeine, Ca2+, and Mg2+ on ryanodine depression of the tension transient in skinned myocardial fibers of the rabbit.

Ryanodine, a blocker for Ca(2+)-release channels of the sarcoplasmic reticulum (SR Ca(2+)-release channels), induces depression of myocardial contraction in isolated intact muscle, which is consistent with depression of the caffeine-induced tension transient in skinned muscle fibers. In isolated SR, ryanodine binds to a specific receptor with high affinity, and this binding is enhanced by caffeine and increasing Ca2+ and decreased by increasing Mg2+. The aim of this study was to test the hypothesis that depression of myocardial contraction is mediated by changes in ryanodine-receptor binding properties. Accordingly, factors (caffeine, Ca2+, and Mg2+) affecting ryanodine-receptor binding properties in the isolated SR membrane were studied in skinned myocardial fibers from adult rabbits. The depression of the caffeine-induced tension transient by ryanodine (ryanodine depression) influenced by these three factors was measured. In a dose-dependent manner, increasing caffeine or Ca2+ concentrations enhanced the ryanodine depression. The concentrations for 50% ryanodine depression (IC50) approximated 7 mM for caffeine, and pCa 5.25 for Ca2+. When 1 microM ryanodine and 25 mM caffeine were combined, ryanodine depression was independent of Ca2+ at low Ca2+ concentrations (20%-30% at pCa greater than 8 and 7.5) and was a direct function of Ca2+ at higher concentrations (pCa 7.5-6.0 with IC50 approx. pCa 6.75). In contrast, increasing Mg2+ reduced the ryanodine depression with IC50 approximately equal to pMg 3.3. In conclusion, the caffeine- or Ca(2+)-enhanced, and Mg(2+)-reduced ryanodine depression observed in this study is consistent with known ryanodine-receptor binding properties.

Animals↗
PubMed1990

Recombinagenicity of caffeine for Candida albicans.

Caffeine at concentrations of 0.5 x 10(-2) M or higher inhibited cell replication and induced gene segregations in Candida albicans cultured on defined complete medium. Both responses increased incrementally with increasing caffeine concentrations, and were more severe during incubation at 37 degrees C than 25 degrees C; at 37 degrees C, caffeine levels above 1.5 x 10(-2) M caused cellular inactivation. Caffeine effects occurred only under conditions permitting cell growth, and their magnitudes were greater for unbudded than budding cells, were influenced by cellular genetic backgrounds, and were unaffected by the presence of adenine in the medium. Evaluations of segregations for recessive auxotrophic markers of a four member linkage group carried heterozygously in a cis arrangement in treated cells established that induced segregants arise through either reciprocal or nonreciprocal recombinations. The frequency distributions of classes of reciprocal and nonreciprocal recombinants for these markers conformed with those previously obtained following induction by ultraviolet radiation, indicating that the probabilities of recombinational events within the chromosomal regions defined by the markers are not biased by the differences in kinds of initial DNA lesions caused by the two recombinagens. A panel of four protoplast fusion hybrids considered deficient for DNA repair because of enhanced susceptibilities to UV induced cellular inactivation and mitotic recombination exhibited corresponding increased sensitivities to caffeine, signifying that DNA damage induced by caffeine is subject to repair. Caffeine did not affect behavior of a variant strain exhibiting high frequency phenotypic switching between minute smooth and large rough colonial forms, and no evidence for mutagenicity of the drug was obtained with systems for detection of forward or reverse mutations. The mechanism of caffeine's recombinagenicity, and the implications of that property for genetic studies of C. albicans are discussed.

Adenine↗
PubMed1985

Impairment of caffeine clearance by chronic use of low-dose oestrogen-containing oral contraceptives.

The effect of chronic (greater than 3 months) administration of low-dose oestrogen-containing (less than 50 micrograms oestrogen) oral contraceptives (OCS) on the pharmacokinetics of caffeine has been examined in a treated females matched with 9 non-smoking, drug-free, healthy control females of similar age, weight and ethnic origin. Each subject received 162 mg caffeine base orally after an overnight fast. OCS subjects had a prolonged elimination half-life of caffeine, (mean 7.88 h vs 5.37 h in the controls). This was the result of marked impairment of the plasma clearance of caffeine (1.05 vs 1.75 ml/min/kg, respectively) with no change in apparent volume of distribution (0.685 in OCS vs 0.7501/kg in the control group). The absorption parameters determined were peak plasma caffeine concentration (3.99 vs 4.09 micrograms/ml) and time to peak concentration after drug administration (1.52 vs 0.79), which was moderately prolonged in OCS users. Thus, caffeine clearance, previously reported to be a specific marker of cytochrome P-448 activity in man, is decreased by chronic OCS use. This suggests that OCS may cause significant impairment of this enzyme activity as assessed in vivo. With chronic caffeine consumption, OCS users are predicted to have an increased steady-state plasma caffeine concentration as compared to non-OCS users.

Adult↗
PubMed1984

Caffeine-induced calcium release from isolated sarcoplasmic reticulum of rabbit skeletal muscle.

The essential conditions for the Ca2+ releasing action of caffeine from isolated sarcoplasmic reticulum (SR) of rabbits were evaluated by an investigation into the effects of Ca2+, Mg2+, MgATP2-, and ATP concentration, ionic strength, and degree of loading. The heavy fraction (4,500 X g) of the reticulum was used. Except for the study on degree of loading, 0.2 mg protein X ml-1 SR was loaded actively with 0.02 mM 45CaCl2, resulting in greater than 90 nmol X mg protein -1 at steady state, and then the effects of various parameters with or without (control) caffeine were tested. It was found that (1) caffeine induces a transient, dose-dependent release of Ca2+, (2) the absolute amount of Ca2+ released by caffeine increases with the Ca2+ load of the SR, (3) increasing the ionic strength (mu) from 0.09 to 0.3 lowers the threshold concentration of caffeine, (4) the SR is refractory to a repeated challenge by a caffeine concentration causing maximal effect, (5) caffeine-induced Ca2+ release increases with increasing (a) external Ca2+ concentrations up to 5 microM total Ca2+ (or 3 microM free Ca2+) and (b) free ATP concentrations up to 0.45 mM, and (6) caffeine-induced Ca2+ release is not affected by changes of either the Mg2+ or the MgATP2- concentration.

Adenosine Triphosphate↗
PubMed1992

Caffeine increases maximal anaerobic power and blood lactate concentration.

The aim of this study was to specify the effects of caffeine on maximal anaerobic power (Wmax). A group of 14 subjects ingested caffeine (250 mg) or placebo in random double-blind order. The Wmax was determined using a force-velocity exercise test. In addition, we measured blood lactate concentration for each load at the end of pedalling and after 5 min of recovery. We observed that caffeine increased Wmax [964 (SEM 65.77) W with caffeine vs 903.7 (SEM 52.62) W with placebo; P less than 0.02] and blood lactate concentration both at the end of pedalling [8.36 (SEM 0.95) mmol.l-1 with caffeine vs 7.17 (SEM 0.53) mmol.l-1 with placebo; P less than 0.01] and after 5 min of recovery [10.23 (SEM 0.97) mmol.l-1 with caffeine vs 8.35 (SEM 0.66) mmol.l-1 with placebo; P less than 0.04]. The quotient lactate concentration/power (mmol.l-1.W-1) also increased with caffeine at the end of pedalling [7.6.10(-3) (SEM 3.82.10(-5)) vs 6.85.10(-3) (SEM 3.01.10(-5)); P less than 0.01] and after 5 min of recovery [9.82.10(-3) (SEM 4.28.10(-5)) vs 8.84.10(-3) (SEM 3.58.10(-5)); P less than 0.02]. We concluded that caffeine increased both Wmax and blood lactate concentration.

Adult↗
PubMed1995

Caffeine-induced locomotor activity: possible involvement of GABAergic-dopaminergic-adenosinergic interaction.

Caffeine (10-40 mg/kg, p.o.) enhanced locomotor activity (LA). Administration of GABA antagonist, bicuculline (0.5-1.0 mg/kg, i.p.), potentiated this caffeine-induced increase of LA, as well as LA of control rats. Treatment with the GABA agonist, muscimol (0.25-1 mg/kg, i.p.) or dopaminergic antagonist, haloperidol (0.25-1 mg/kg, i.p.) or muscarinic receptor blocker, atropine (3.75-5 mg/kg, i.p.), or inhibitor of acetylcholine esterase physostigmine (0.05-0.30 mg/kg, i.p.) or nicotine (0.5-1.5 mg/kg, i.p.) an nicotinic receptor agonist all decreased the LA of both caffeine-treated and control rats. Haloperidol-induced reduction in caffeine-induced increase in LA was found to be withdrawn with higher dose of caffeine. The dopamine agonist L-Dopa (75-150 mg/kg, p.o.) along with carbidopa (10 mg/kg, p.o.) increased the LA in control rats and potentiated the LA of caffeine treated rats. The haloperidol attenuated the bicuculline-induced increase in LA and atropine or physostigmine attenuated the bicuculline or L-Dopa + carbidopa-induced increase in LA in both caffeine treated and control rats when those drugs were administered concomitantly with bicuculline or L-Dopa+carbidopa. These results suggest that (a) the GABAergic system has direct role in the regulation of LA, and (b) caffeine potentiates LA by antagonism of the adenosine receptor and activation of the dopaminergic system which, in turn, reduces GABAergic activity through the reduction of cholinergic system.

Animals↗
PubMed1986

Effect of caffeine on ceftriaxone disposition and plasma protein binding in the rat.

Previous studies have shown that caffeine can affect drug kinetics by altering drug binding to plasma protein, drug absorption, or drug distribution. In this study, the effect of caffeine on the in vivo protein binding and the disposition of ceftriaxone (a highly protein-bound cephalosporin) were investigated in the rat. Ceftriaxone 100 mg/kg and caffeine 20 mg/kg were i.v. injected via the tail vein and ceftriaxone in plasma, plasma filtrate, urine, feces, and tissues (brain, heart, kidney, liver, gut, lung, and muscle) was assayed by HPLC with UV detection. The fraction of free ceftriaxone in plasma ranged from 5.6 to 32.8% of total ceftriaxone (3-347 micrograms/ml) without caffeine and showed no alteration by caffeine. The total amount of ceftriaxone excreted in urine and feces was increased significantly (p less than 0.05) from 13.1 +/- 1.8 mg (mean +/- SD, 54.6% of total) to 15.3 +/- 1.1 mg (63.8% of total) by caffeine coadministration. The terminal half-life of ceftriaxone in plasma was shortened from 59 to 47 min, and the area under the plasma drug concentration-time curve (AUC) was reduced from 612 to 516 micrograms hr/ml. Although the peak drug concentrations and the times of peak concentration of ceftriaxone in tissues were not altered by caffeine administration, the elimination of ceftriaxone was increased, as indicated by generally shorter half-lives (decreases ranged from 17.5% in liver to 34.2% in brain) and lower AUC values (from 9.0% in heart to 54.5% in brain). These results suggest that caffeine does not alter the protein binding of ceftriaxone, but enhances the elimination of ceftriaxone in the rat.

Animals↗
PubMed1983

Comparative pharmacokinetics of caffeine in young and elderly men.

The pharmacokinetic behavior of caffeine was compared in a group of eight healthy young men aged 20.5 +/- 2.0 years (mean +/- SD), and in a group of eight healthy, elderly men aged 71.2 +/- 3.9 years. Each subject was given a 5 mg/kg dose of caffeine as either an aqueous oral solution or an intravenous infusion over 30 min using a randomized crossover design. Plasma and urine samples were collected for 24 hr following each dose and analyzed for caffeine content using high-performance liquid chromatography. The peak times (tmax), peak concentrations (Cmax), and the percentage of the peroral dose systemically available, F(%), were essentially identical in both age groups, indicating that caffeine was absorbed rapidly and completely after peroral administration. These results also indicated that the first-pass metabolism observed in rats following the peroral administration of caffeine does not occur in either human group studied here. The elimination of caffeine during its terminal disposition phase was log-linear. Several between-group comparisons of other pharmacokinetic parameters were made. Although the average elimination rate constant was greater in the elderly, the difference did not reach statistical significance, possibly because of the considerable intersubject variability in the elimination rate of caffeine, with half-lives ranging from 2.27 to 9.87 hr. The average apparent volume of distribution was significantly lower in the elderly subjects while the clearances were slightly, but not significantly, larger in the elderly subjects. It appears that most aspects of the pharmacokinetic behavior of caffeine are very similar in young and elderly men.

Adolescent↗
PubMed1996

Caffeine enhancement of electrical activity through direct blockade of inward rectifying K+ currents in GH3 rat anterior pituitary cells.

Treatment of rat anterior pituitary GH3 cells with caffeine causes a reversible enhancement of electrical activity superimposed over a depolarization of the plasma membrane potential. Similar results are obtained with theophylline, but not with isobutylmethylxanthine or forskolin. The effects of caffeine are not related to Ca2+ liberation from intracellular stores since they are not affected by incubation of the cells with ryanodine or thapsigargin. Furthermore, caffeine-induced hyperpolarization of the membrane is not detectable even in cells in which Ca2+ liberation from inositol 1,4,5-trisphosphate-sensitive compartments produces a prominent transient hyperpolarization in response to thyrotropin-releasing hormone. Reductions of Ca2+-dependent K+ currents caused by partial block of L-type Ca2+ channels by caffeine are not sufficient to explain the effects of the xanthine, since the results obtained with caffeine are not mimicked by direct blockade of Ca2+ channels with nisoldipine. GH3 cell inwardly rectifying K+ currents are inhibited by caffeine. Studies on the voltage dependence of the caffeine-induced effects indicate a close correlation between alterations of electrical parameters and reported values of steady-state voltage dependence of inactivation of these currents. We conclude that, as previously shown for thyrotropin-releasing hormone, modulation of inwardly rectifying K+ currents plays a major role determining the firing rate of GH3 cells and its enhancement by caffeine.

Animals↗
PubMed1992

Forced-choice versus free-choice procedures: caffeine self-administration in humans.

Methodological comparisons of procedures for drug self-administration are rare. In studies examining the reinforcing effect of caffeine in humans, caffeine self-administration usually has been inferred from performance under forced-choice procedures. In the present experiment, caffeine self-administration via coffee was compared under forced-choice and free-choice conditions; i.e., when subjects were and were not required to use a minimum number of coffees. Ten moderate coffee drinkers (2-7 cups/day) were assigned to forced- and free-choice conditions using a randomized cross-over design. Under each choice condition, subjects completed six independent, double-blind trials, consisting of a 2-day exposure period followed by a 2-day test period. During exposure, subjects consumed either decaffeinated or caffeinated (100 mg/serving) coffee on day 1 and the other coffee on day 2. During the test period, subjects had concurrent access to the same decaffeinated and caffeinated coffees. Under the forced-choice condition, subjects were required to drink at least four cups of coffee per day during the test period. Under the free-choice condition, subjects did not have a minimum-cup requirement. In general, the relative rate at which subjects self-administered caffeinated versus decaffeinated coffee was similar across choice conditions, even though subjects self-administered significantly fewer cups of both coffee types under the free-choice than the forced-choice condition. These results suggest that, at least for caffeine, forced-choice and free-choice procedures produce comparable results. Whether this finding generalizes to a context in which caffeine or another drug is more robustly self-administered, remains to be determined.

Adult↗