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1.
In the presence of glutathione, a homogenate of rat intestinal mucosa transforms linoleic acid hydroperoxide (LOOH) into the corresponding alcohol (LOH). The Km of the enzyme involved (a glutathione peroxidase) is 5.7 × 10?6m. The specific activity, measured as generated LOH, was found to be 0.058 μmol/mg protein/min, six times lower than that of the liver. A mitochondrial supernatant of the mucosal homogenate had 1.5 times the activity of the initial homogenate. The reduction of 1 mol LOOH requires 2 mol glutathione. Besides this enzymatic deperoxidation, 5% of the LOOH was decomposed in both the intestinal mucosa and liver by a non-enzymatic pathway, probably involving the Fe3+ of the haemoproteins. 相似文献
2.
Hervé Goudonnet Bernard Chaillot Roger Truchot Raymond Michel 《Biochemical pharmacology》1975,24(18):1687-1694
3,5,3'-Triiodo-thyroformic (TF3), 3,5,3'-triiodo-thyroacetic (TA3) and 3,5,3'-triiodo-thyropropionic (TP3) acids, which are structural analogs of 3,5,3'-triiodo-L-thyronine (LT3), have been found to inhibit beef liver glutamate dehydrogenase (GlDH), horse liver alcohol dehydrogenase (ADH) and pig heart isocitrate dehydrogenase (ICDH), but different mechanisms are involved. TF3, TA3 and TP3 inhibit GlDH non competitively with respect to NADP, but competitively with ADP-ribose, an activator of GlDH. For the inhibition of ADH, the three iodinated derivatives compete with NAD and ADP-ribose; ADP-ribose being itself competitive with NAD. So, it appears that TF3, TA3 and TP3 interfere with the coenzyme binding by blocking the binding site of the ADP-ribose portion of the coenzyme. These iodinated inhibitors quench the enhanced fluorescence which originates from the enzyme-coenzyme binding. However, in the case of the GlDH, TP3 exhibit an opposite effect. E.s.r. studies showed that ICDH inhibition by TA3, did not result from the chelation of Mn2+, but that TA3 impaired binding of Mn2+ to the enzyme and coenzyme. 相似文献
3.
L A O'Tuama C S Kim J T Gatzy M R Krigman P Mushak 《Toxicology and applied pharmacology》1976,36(1):1-9
The central neural distribution of radiolabeled lead nitrate (210Pb) and total lead concentrations were investigated in adult pigs after intravenous injection of the tracer. Control animals were fed ad libitum, whereas lead encephalopathy was induced by feeding other animals 165 mg lead carbonate daily for 6 days. Lead was not detected in choroid plexus (CP). (Average concentration in control animals <1.2 μg/g; <1.5 μg/g in poisoned animals.) Brain lead concentrations averaged 0.095 ± 0.016 μg/g wet weight in control nimals and 0.427 ± 0.067 μg/g in poisoned animals. CP concentrated the pulsed radiolabel more than 70 times as avidly as brain, and in meninges and ependyma the concentration of 210Pb also exceeded markedly that occurring in brain. The high initial uptake of radiolead by CP indicates that this organ may act as a “sink”, tending to reduce lead entry into CSF and brain. Pretreatment with ouabain iv (1.6 – 1.7 × 10?9 mol/kg) reduced significantly 210Pb accumulation by CP and by brain 5 and 60 min after label injection in control animals but not in lead-poisoned animals. These results suggest that active transport of cations by the barrier tissues may influence the central neural distribution of lead. 相似文献
4.
The complex cardiovascular actions of the venoms of three North African scorpions and of the toxins I and II isolated from one of them (Aa) are characterized by: (1) an action on the sympathetic ganglia. There is a release of catecholamines from nerve endings which is responsible for the hypertension, peripheral vasoconstriction, lachrymation, salivation, breathing spasms and an indirect positive inotropic effect. Later, ganglionic blockade (except for toxin I) produces a block of the vascular tone leading to hypotension. (2) An action on the heart. There was noted a direct inotropic effect, bradycardia and a toxic effect (negative inotropism and arrhythmia) leading to fibrillation. There is an involvement of the muscarinic intracardiac receptors and particularly of the beta-adrenergic receptors. The venom of the scorpion Androctonus australis is different from the other two venoms in that it produces the strongest discharge of catecholamines and it contains toxin I which differs from toxin II in that it has no ganglionic-blocking effect: the bradycardia by toxin I is also greater than with toxin II and its cardiotoxic action is hardly antagonized by propranolol. 相似文献
5.
The mechanism of action of 4-iodosalicylic acid on oxidative phosphorylation in isolated rat liver mitochondria was studied. 4-Iodosalicylic acid reversed oligomycin inhibition of respiration in state 3 mitochondria. In a state uncoupled by 2,4-dinitrophenol. however, the O2 consumption rate was lowered by the iodocompound. The Lineweaver Burk plot of 4-iodosalicylic acid inhibition of the rate of O2 consumption with variable concentrations of succinate in the presence of ADP, was represented by straight lines. The inhibition was noncompetitive. With mitochondria in state 3, double wavelength spectrophotometric analysis of oxidoreduction states of respiratory coenzymes, showed that 4-iodosalicylic acid increased the oxidation of all components of the electron transport chain, in spite of the fact that it inhibited the oxygen consumption rate. In conclusion 4-iodosalicylic acid may be considered as an uncoupling agent, for its effects are similar in some aspects to those of 2,4-dinitrophenol. It is possible that there are at least two distinct sites at which the iodophenol can inhibit respiration; one site is probably in the respiratory chain and the other, more important, related with the coupling of high-energy intermediates. 相似文献
6.
Hansen DK Scott DO Otis KW Lunte SM 《Journal of pharmaceutical and biomedical analysis》2002,27(6):945-958
The studies presented in this report were designed to assess the correlation of the bovine brain microvessel endothelial cell (BBMEC) apparent permeability coefficient (Papp) and in vivo BBB penetration using microdialysis sampling. A mathematical model was developed to describe the relationship of brain extracellular fluid (ECF) concentration to free drug in plasma. The compounds studied have a broad range of physico-chemical characteristics and have widely varying in vitro and in vivo permeability across the blood–brain barrier (BBB). BBMEC permeability coefficients vary in magnitude from a low of 0.9×10−5 cm/s to a high value of 7.5×10−5 cm/s. Corresponding in vivo measurements of BBB permeability are represented by clearance (CLin) into the brain ECF and range from a low of 0.023 μl/min/g to a high of 12.9 μl/min/g. While it is apparent that in vitro data from the BBMEC model can be predictive of the in vivo permeability of a compound across the BBB, there are numerous factors both prior to and following entry into the brain which impact the ultimate uptake of a compound. Even in the presence of high BBB permeability, factors such as high plasma protein binding, active efflux across the BBB, and metabolism within the CNS can greatly limit the ultimate concentrations achieved. In addition, concentrations in the intracellular space may not be the same as concentrations in the extracellular space. While these data show that the BBMEC permeability is predictive of the in vivo BBB permeability, the complexity of the living system makes prediction of brain concentrations difficult, based solely on the in vitro measurement. 相似文献
7.
Carai MA Colombo G Reali R Serra S Mocci I Castelli MP Cignarella G Gessa GL 《European journal of pharmacology》2002,441(3):157-163
The aliphatic alcohol 1,4-butanediol in converted into gamma-hydroxybutyric acid (GHB) via two enzymatic steps: first, it is oxidised by alcohol dehydrogenase in gamma-hydroxybutyraldehyde; second, the latter is transformed, likely by aldehyde dehydrogenase, into GHB. Initially, the present study compared the sedative/hypnotic effect of GHB and 1,4-butanediol, measured as loss of righting reflex. 1,4-Butanediol was more potent than GHB, presumably because of a more rapid penetration of the blood brain barrier. Further alcohol dehydrogenase inhibitors, 4-methylpyrazole and ethanol, totally prevented the sedative/hypnotic effect of 1,4-butanediol; the aldehyde dehydrogenase inhibitor disulfiram partially blocked the sedative/hypnotic effect of 1,4-butanediol. Finally, the sedative/hypnotic effect of 1,4-butanediol was antagonised by the GABA(B) receptor antagonists, SCH 50911 [(2S)(+)-5,5-dimethyl-2-morpholineacetic acid] and CGP 46381 [(3-aminopropyl)(cyclohexylmethyl)phosphinic acid], but not by the putative GHB receptor antagonist NCS-382 (6,7,8,9-tetrahydro-5-hydroxy-5H-benzocyclohept-6-ylideneacetic acid), indicating that it is mediated by GABA(B) but not GHB receptors. Taken together, these results suggest that the sedative/hypnotic effect of 1,4-butanediol is mediated by its conversion in vivo into GHB which, in turn, binds to GABA(B) receptors. Accordingly 1,4-butanediol, unlike GHB, failed to displace [(3)H]GHB and [(3)H]baclofen in brain membranes. 相似文献
8.
Lin JH 《Current drug metabolism》2008,9(1):46-59
For drugs that directly act on targets in the central nervous system (CNS), sufficient drug delivery into the brain is a prerequisite for drug action. Systemically administered drugs can reach CNS by passage across the endothelium of capillary vasculatures, the so-called blood-brain barrier (BBB). Literature data suggest that most marketed CNS drugs have good membrane permeability and relatively high plasma unbound fraction, but are not good P-glycoprotein (P-gp) substrates. Therefore, it is important to use the in vitro parameters of P-gp function activity, membrane permeability and plasma unbound fraction as key criteria for lead optimization during the early stage of drug discovery. Evidence from preclinical and clinical studies suggests that drug concentration in cerebrospinal fluid (CSF) appears to be reasonably accurate in predicting unbound drug concentration in the brain. Therefore, CSF can be used as a useful surrogate for in vivo assessment of CNS exposure and provides an important basis for the selection of drug candidates for entry into development. However, it is important to point out that CSF drug concentration is not always an accurate surrogate for predicting unbound drug concentration in the brain. Depending on the physicochemical properties of drugs and the site/timing of CSF sampling, the unbound drug concentration at the biophase within the brain could differ significantly from the corresponding CSF drug concentration. 相似文献
9.
王一萍 《中国新药与临床杂志》1989,(4)
氯硝西泮是苯并二氮杂(艹卓)类衍生物,有抗惊厥和镇静的作用,本文用氯硝西泮与甲喹酮对46例失眠病人进行了对照研究,氯硝西泮组有效率达81%,其效果优于甲喹酮,在服用过程中,未见明显副反应。结果表明:氯硝西泮是一种有效的安眠镇静药。 相似文献
10.
Gerace E Ciccotelli V Rapetti P Salomone A Vincenti M 《Journal of analytical toxicology》2012,36(6):452-456
Chloralose (alpha-chloralose) is a poisonous substance currently used as a rodenticide or avicide. It has primarily been used in Europe since 1893 as a human and veterinary hypnotic agent. Chloralose is a central nervous system depressant also acting as a stimulant on spinal reflexes. In the present case, a 24-year-old man was found dead in his bedroom near vomit residues. Several items were seized from the scene, including an empty bottle of Murex 50 g (α-chloralose), sold in Italy as rodenticide. Postmortem examination revealed no evidence of natural disease or trauma. Heart blood, urine, gastric contents, vitreous humour, brain, bile and liver were collected and submitted for toxicological analysis. Several extraction procedures and a specific liquid chromatography-tandem mass spectrometry protocol were purposely developed and validated. Chloralose was found in blood at a concentration of 65.1 mg/L and high levels were also detected in the gastric contents, confirming its ingestion shortly before the man's death. The distribution of chloralose in the body was evaluated by analyzing urine, vitreous humour, brain, bile and liver specimens. Quantitation of chloralose in several body fluids and tissues adds new data about the distribution of this chemical in the human body after massive ingestion. 相似文献
11.
Brain extracellular fluid (ECF) concentration of YM992, a novel antidepressant, was determined using brain microdialysis to investigate the high partition of this drug to the brain after systemic administration to rats. Plasma, cerebrospinal fluid (CSF), ECF and brain concentrations were determined at the steady-state after intravenous infusion to rats. The concentration ratio of brain to plasma at the total concentration base was 71.3, while those of ECF to plasma and CSF to plasma at the free concentration base were comparable. The distribution volume in brain was 375 ml/g brain and in vitro binding of YM992 to rat brain was 98.1-98.5%, suggesting a high binding in the brain. The carotid artery injection study showed that the brain uptake index of YM992 was 141%, furthermore, the uptake clearance into brain after i.v. dosing to rats was 0.6 ml/min/g brain, indicating a high permeability at the blood-brain barrier (BBB). These findings suggest that the high partition of YM992 to rat brain is attributed to its high level of binding in the brain as well as its high permeability at the BBB. 相似文献
12.
《Journal of labelled compounds & radiopharmaceuticals》2004,47(9):531-542
4‐Fluoro‐N‐{2‐[4‐(6‐trifluoromethylpyridin‐2‐yl)piperazin‐1‐yl]ethyl}benzamide is a full 5‐HT1A agonist with high affinity (pKi=9.3), selectivity and a c log P of 3.045. The corresponding PET radioligand 4‐[18F]fluoro‐N‐{2‐[4‐(6‐trifluoromethylpyridin‐2‐yl)piperazin‐1‐yl]ethyl}benzamide was synthesized by nucleophilic aromatic substitution on the nitro precursor. The fluorinating agent K[18F]F/Kryptofix 2.2.2 was both dried (9 min, 700 W) and incorporated in the precursor (5 min, 700 W) using a commercially available microwave oven. In a total synthesis time of 60 min, an overall radiochemical yield of 18% (SD=5, n=7, EOS) was obtained. Radiochemical purity was always higher than 99% and specific activity always higher than 81.4 GBq/µmol (2.2 Ci/µmol). Initial brain uptake in mice was 2.19% ID (5.47% ID/g, 2 min) but decreased rapidly (0.17% ID, 0.45% ID/g (60 min)). During the first 20 min p.i., radioactivity concentration of the brain was significantly higher than that of blood demonstrating good brain entry of the tracer. Copyright © 2004 John Wiley & Sons, Ltd. 相似文献
13.
Physical dependence to sedative/hypnotic drugs is not an uncommon clinical problem. The withdrawal syndrome is analogous to alcohol withdrawal, except the duration of the syndrome occurs over a longer period of time with the symptoms being less intense than generally encountered with alcohol. The potential for withdrawal reactions is probably greater for the shorter-acting agents than the longer-acting drugs. Potentially dependent sedative/hypnotic users require stabilization of their symptoms initially, followed by tolerance testing. If tolerant, the patients should be withdrawn using either a long-acting sedative/hypnotic (e.g., diazepam) or phenobarbital. Compared to other benzodiazepines and barbiturates, diazepam appears to be the drug of choice for treating dependent patients. Diazepam is rapidly absorbed and distributed to the brain and therefore useful for stabilization and tolerance testing. It is metabolized on chronic administration to a long-acting metabolite, desmethyldiazepam, which makes the drug ideal for a tapered withdrawal schedule. 相似文献
14.
Svetlana M Stamatovic Richard F Keep Anuska V Andjelkovic 《Current Neuropharmacology》2008,6(3):179-192
The blood-brain barrier (BBB) is a highly specialized structural and biochemical barrier that regulates the entry of blood-borne molecules into brain, and preserves ionic homeostasis within the brain microenvironment. BBB properties are primarily determined by junctional complexes between the cerebral endothelial cells. These complexes are comprised of tight and adherens junctions. Such restrictive angioarchitecture at the BBB reduces paracellular diffusion, while minimal vesicle transport activity in brain endothelial cells limits transcellular transport. Under normal conditions, this largely prevents the extravasation of large and small solutes (unless specific transporters are present) and prevents migration of any type of blood-borne cell. However, this is changed in many pathological conditions. There, BBB disruption (“opening”) can lead to increased paracellular permeability, allowing entry of leukocytes into brain tissue, but also contributing to edema formation. In parallel, there are changes in the endothelial pinocytotic vesicular system resulting in the uptake and transfer of fluid and macromolecules into brain parenchyma. This review highlights the route and possible factors involved in BBB disruption in a variety of neuropathological disorders (e.g. CNS inflammation, Alzheimer’s disease, Parkinson’s disease, epilepsy). It also summarizes proposed signal transduction pathways that may be involved in BBB “opening”. 相似文献
15.
S Capello L Henderson F DeGrazia D Liberato W Garland C Town 《Drug metabolism and disposition》1990,18(2):190-196
Flurazepam (F) is an extensively prescribed hypnotic (Dalmane) whose in vivo activity has been suggested to be due to its primary metabolites, hydroxyethyl flurazepam (HEF) and N-desalkylflurazepam (DAF). In order to determine the intrinsic pharmacologic activity of F, mice were administered various doses of the cytochrome P-450 suicide inactivator, 1-aminobenzotriazole (ABT), 1 hr before the ip administration of 1 mg/kg 14C-F. One hr after 14C-F, 70 mg/kg pentylenetetrazole was administered iv and the mice were observed for convulsions. F alone offered no protection from convulsion (mean brain concentrations were 3.9, 32, and 11 ng/g for F, DAF, and HEF, respectively). F with 25 mg/kg ABT also offered no protection despite a 6-fold increase in brain concentrations of F. F with 100 mg/kg ABT offered a 57% protection from convulsions (mean brain concentrations were 99, 62, and 41 ng/g for F, DAF, and HEF, respectively). One mg/kg F with 400 mg/kg ABT offered 100% protection from convulsions (brain concentrations were 190, 47, and 18 ng/g for F, DAF, and HEF, respectively). These data indicate that F has intrinsic pharmacologic activity which must be considered when evaluating the pharmacodynamics of F. 相似文献
16.
Vimala H. Sethy 《Naunyn-Schmiedeberg's archives of pharmacology》1978,301(3):157-161
Summary Pentobarbital (30 and 60 mg/kg) and chloral hydrate (300 and 600 mg/kg) administered in anesthetic/hypnotic doses produced significant increases in acetylcholine concentration in the cerebral cortex, striatum, hippocampus and brainstem. Hypnotic/anxiolytic agents like diazepam, flurazepam (100 mg/kg each) and triazolam (30 mg/kg) significantly increased the acetylcholine concentration only in the cerebral cortex and striatum. Alprazolam and ketazolam had no significant effect on regional distribution of acetylcholine in the brain. The results have been discussed with respect to the role of central cholinergic system in anesthetic and hypnotic actions of these drugs. 相似文献
17.
Acid metabolites of monoamines in avian brain; effects of probenecid and reserpine 总被引:6,自引:4,他引:2
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1. The concentration of the dopamine (DA) metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) in the anterior part of the nucleus basalis of pigeon brain was found to be 0.17 +/- 0.01 mug/g, which is about one-fifth of the concentration of homovanillic acid (HVA) in this region. In the chicken, the concentration of HVA in the (entire) nucleus basalis was 0.06 +/- 0.006 mug/g, lower than in any other species examined, and giving a ratio of DA to HVA of about 50. The concentration of DOPAC in the 8 day old chick was 0.053 +/- 0.002 mug/g.2. Probenecid, 200 mg/kg intramuscularly, doubled the content of DOPAC in the nucleus basalis of the pigeon and increased the concentration of HVA in both the pigeon and the chicken by a factor of 4 to 5. These findings demonstrate the existence, in avian brain, of an active transport mechanism for the removal of acidic substances and explain the low concentrations of the acids found in bird brain.3. A method is described for the estimation of 5-hydroxytryptamine (5-HT) and 5-hydroxyindolylacetic acid (5-HIAA) in the same tissue sample. Probenecid caused an increase in the 5-HIAA content but produced no change in the 5-HT content of the nucleus basalis of pigeon brain.4. Reserpine caused a fall in the content of acidic DA metabolites in the nucleus basalis of the pigeon. The effect was more pronounced after raising the concentration of these acids with probenecid.5. Treatment of pigeons with pargyline (100 mg/kg 17 hr before decapitation) did not significantly increase the DA content of the nucleus basalis, but it prevented to some extent the loss in DA caused by reserpine.6. Pigeons and chickens were sedated by probenecid. The deepest sedation occurred at about the same time as the greatest increase in the acidic amine metabolites in the brain.7. Intracisternal injection of HVA in the pigeon and intravenous injection of large amounts of HVA, DOPAC, 5-HIAA or 3,4-dimethoxyphenylacetic acid into newly hatched chicks did not produce any sedation or other effects on behaviour. In contrast, injection of sodium gamma-hydroxybutyrate caused paralysis followed by prostration and eye closure.8. Estimation of the concentration of HVA in the brain of the young chick after intravenous injection of the acid (100 mg/kg) showed that the concentration was of the same order of magnitude as it is in animals given probenecid; this suggests that the sedation which follows probenecid is not related to the accumulation of acidic amine metabolites. 相似文献
18.
Rationale Acetaldehyde, the first metabolite of ethanol, was recently suggested to contribute to many behavioral effects of ethanol, although few studies have directly investigated the behavioral effects of acetaldehyde itself.Objectives The aim of the present study was to characterize the locomotor, hypnotic, anxiolytic-like and amnesic effects of acetaldehyde in C57BL/6J mice.Methods Increasing doses of acetaldehyde (0–300 mg/kg) were injected intraperitoneally and their effects on a series of representative behaviors were investigated. The locomotor effects of acetaldehyde were measured in activity boxes. The duration of the loss of righting reflex was used as an index of the hypnotic effects of acetaldehyde. The anxiolytic-like effects of acetaldehyde were tested with an elevated plus-maze and the amnesic effects with the one-trial passive avoidance test. Finally, brain and blood acetaldehyde concentrations were assessed.Results Acetaldehyde induced a significant hypolocomotor effect at 170 mg/kg and higher doses. In addition, the hypnotic effects of acetaldehyde were demonstrated by a loss of righting reflex after the administration of 170 and 300 mg/kg acetaldehyde. The elevated plus-maze showed that acetaldehyde does not possess anxiolytic-like properties. Finally, acetaldehyde (100–300 mg/kg) dose-dependently altered memory consolidation as shown by a reduced performance in the passive avoidance test.Conclusions The present results show that acetaldehyde induces sedative, hypnotic and amnesic effects, whereas it is devoid of stimulant and anxiolytic-like properties in C57BL/6J mice. However, the behavioral effects of acetaldehyde after intraperitoneal administration were apparent at very high brain concentrations. The present results also indicate that acetaldehyde is unlikely to be involved in the anxiolytic properties of ethanol in mice. 相似文献
19.
Rationale Toluene exposure during brain growth spurt has been shown to elevate the seizure susceptibility induced by N-methyl-d-aspartate (NMDA). In the present study, behavioral responses to NMDA antagonists were studied to determine whether neonatal
toluene exposure produces residual deficits in the NMDA glutamatergic system controlling behaviors. We also investigated if
the effect of toluene exposure depends strongly on the developmental stage.
Objectives The long-term effects of neonatal and adolescent toluene exposure on MK-801 and/or ketamine-induced hyperlocomotor activity,
motor coordination, hypnotic response, and cognitive deficits in early adulthood were compared.
Methods Sprague–Dawley male rats were treated with toluene (500 mg/kg i.p.) daily over postnatal day (PN) 4–9 or 25–30. Locomotor
activity was analyzed in a computerized open-field system, motor coordination was measured by rotarod, hypnotic response was
tested by loss of righting reflex, and long-term memory was assessed with the inhibitory avoidance learning task during PN
56–60.
Results Toluene exposure during brain growth spurt reduced behavioral responses including locomotor activity, motor incoordination,
and hypnosis to MK-801 and/or ketamine, while leaving cognitive deficits in inhibitory avoidance learning tasks unaffected.
No significant change in behavioral responses to NMDA antagonists was observed following adolescent toluene exposure.
Conclusion These results indicate that neonatal but not adolescent toluene exposure produces long-term effects on selective behaviors
induced by NMDA antagonists. Theses findings further support the hypothesis that functional changes in NMDA receptors may
be related to the neurobehavioral dysfunction associated with fetal solvent syndrome. 相似文献
20.
Rationale The transition from adolescence into adulthood is characterized by rapid maturation of brain systems mediating reward and
by increasing experimentation with drugs of abuse including ethanol (EtOH). Previous studies have found marked differences
in sensitivity to the behavioral effects of EtOH in adolescent rats as compared to adults, but relatively few studies have
been conducted in mice.
Objectives The present study examined sensitivity to various behavioral effects of EtOH in C57BL/6J mice at various stages of adolescence/adulthood
(4, 6, 8 weeks old). Ages were compared for locomotor stimulant (open field), anxiolytic-like (elevated plus-maze), memory-impairing
(Pavlovian fear conditioning) and ataxic (accelerating rotarod) effects of EtOH, and the sedative/hypnotic (sleep time) effects
of EtOH and pentobarbital. EtOH self-administration was compared using a two-bottle choice paradigm. Measures of EtOH metabolism
were also obtained.
Results Early adolescent mice exhibited increased sensitivity to locomotor stimulant (1.5 g/kg), anxiolytic-like (1.5 g/kg) and ataxic
(1.5–2.5 g/kg), but not memory impairing (2.0 g/kg), effects of EtOH relative to adults. Early adolescent, and to some extent
peri-adolescent, mice were less sensitive than adults to the sedative/hypnotic effects of EtOH (3.5–4.5 g/kg), but not pentobarbital
(40–50 mg/kg). Early adolescent mice showed lower EtOH preference, but not EtOH consumption, than adults. Blood EtOH concentrations
were higher at early time points and lower at later time points after (3.0 g/kg) EtOH injection in early and peri-adolescents
relative to adults.
Conclusions Present data demonstrate that sensitivity to the acute intoxicating effects of EtOH changes across mouse adolescent development
in a behavior-dependent manner. 相似文献