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Citalopram, a selective 5-HT uptake inhibitor with antidepressant properties, was assessed in three studies in 12 healthy subjects using a battery of EEG, psychological, subjective and symptomatic measures. Study A involved the administration of citalopram, 20 mg and 40 mg, amitriptyline 50 mg and placebo in single dose using a balanced cross-over design. The test battery was applied before, and 1 and 3 h after each drug. Citalopram decreased slow-wave EEG activity whereas amitriptyline increased power in most EEG wavebands. Citalopram increased tapping rate and symbol copying whereas amitriptyline impaired these and other psychomotor tasks. Subjectively, amitriptyline was much more sedative than citalopram and produced more complaints of dry mouth. Study B comprised the administration of citalopram in the usual clinical dose of 40 mg, amitriptyline in the low clinical dose of 75 mg and placebo, each given for 9 nights using a balanced cross-over design. The test battery was applied on the first morning (pre-drug) and on the morning after the last nightly dose. None of the physiological tests showed any drug effects. Subjectively, citalopram was associated with feelings of shaking, nausea, loss of appetite and physical tiredness; amitriptyline produced feelings of shaking, nausea, loss of appetite, dryness of mouth, irritability, dizziness and indigestion; in general, amitriptyline effects were more marked than those of citalopram. Plasma samples were taken on the last day and plasma concentrations of both drugs and their metabolites were found to be in the expected range for the regimens used.(ABSTRACT TRUNCATED AT 250 WORDS)

Ethanol may act at the enkephalinergic receptor level through condensation products such as salsolinol. This fact has been demonstrated by studying the 'in vitro' and 'in vivo' salsolinol interaction on enkephalinergic receptor sites labeled by [3H-Met] enkephalin. The modification induced by chronic ethanol and salsolinol on this neuronal system is a reduction of the affinity of the receptor for its ligand. These data suggest that a down regulation process due to the continuous opiate receptor stimulation occurs after ethanol administration.

Abstract When acetyl ethyl tetramethyl tetralin (AETT), at 10–50 μg/ml, was added to rat liver mitochondria respiring with succinate or with glutamate plus malate as substrate, the rate of mitochondrial respiration increased significantly after an initial lag period, of 2–3 min. AETT also stimulated respiration in the presence of oligomycin, and at higher concentrations of AETT a phase of strongly inhibited respiration followed an initial stimulatory phase. These observations suggest that AETT uncouples oxidative phosphorylation. A diketo derivative (DK) of tetramethyl tetralin also appears to be an uncoupling agent, according to those criteria, and both compounds uncoupled mitochondria from brain as well as liver. DK and many other uncoupling agents, such as hexachlorophene (HCP), produced an immediate burst of respiration, whereas the brief lag after addition of AETT was similar to that seen after addition of triethyltin (TET).

Background: Short‐sleep (SS) mice exhibit higher locomotor activity than do long‐sleep (LS) mice when injected with low doses of ethanol or the noncompetitive N‐methyl‐D‐aspartate receptor (NMDAR) antagonist MK‐801 (dizocilpine). SS mice also have higher densities of brain NMDARs. However, two strains of LS X SS recombinant inbred (RI) mice also show differential activation to ethanol and MK‐801, but have similar numbers of NMDARs. Here we used inbred LS (ILS) and SS (ISS) mice to investigate further the relationship between NMDARs and sensitivity to the stimulant effects of low doses of ethanol.Methods: Open field activity and spontaneous alternations were measured after saline or drug injection. [3H]MK‐801 binding parameters were determined in hippocampus, cortex, striatum, and nucleus accumbens. Extracellular field excitatory postsynaptic potentials (fEPSPs) were recorded in the CA1 region of hippocampal slices.Results: Systemic injection of either ethanol or MK‐801 increased locomotor activity to a greater extent in ISS mice than in ILS mice. The competitive NMDAR antagonist 2‐carboxypiperazin‐4‐yl‐propyl‐1–1phosphonic acid (±CPP) depressed activity of ILS, but not ISS, mice. No strain differences were observed in spontaneous alternations or in the number or affinity of NMDARs in the brain regions examined. Likewise, the magnitudes of hippocampal NMDAR‐mediated fEPSPs were similar in ILS and ISS mice and were inhibited to the same extent by a competitive NMDAR antagonist. However, both ethanol and the NMDAR NR2B receptor antagonist ifenprodil inhibited the late component of hippocampal NMDAR fEPSPs to a greater extent in ISS, than in ILS, mice.Conclusions: Differential ethanol‐ and MK‐801‐induced behavioral activation in ILS and ISS mice was not associated with differences in NMDAR number. Nonetheless, pharmacological differences in hippocampal NMDAR responsiveness suggest that ISS mice express NMDARs that have a greater sensitivity to noncompetitive, but not competitive, NMDAR antagonists. These differences, which may reflect differences in NMDAR subunit composition, could underlie the differential responsiveness to low doses of ethanol in ILS and ISS mice.

Moringa oleifera Lamarck is a species that has long been used in high demand in folk medicine, including for the treatment of epilepsy. Nevertheless, scientific studies demonstrating its anticonvulsant properties and the nature of the bioactive constituents are lacking.The aim of this study was to evaluate the anticonvulsant activities of the Moringa oleifera leaves in non-polar vs. polar extracts using behavioral and electroencephalographic (EEG) analyses in rodents.First, PTZ (80 mg/kg, i.p.)-induced tonic-clonic seizures were assayed via a dose-response (100, 200 and 300 mg/kg, i.p.) evaluation in mice. Then, a dosage of the extracts (100 or 300 mg/kg) and one metabolite (30 mg/kg, i.p.) was selected to evaluate its effect on PTZ (35 mg/kg, i.p.)-induced EEG paroxystic activities in rats compared to the effects of ethosuximide (reference anticonvulsant drug, 100 mg/kg, i.p.). Latent onset of the first paroxystic spike, first seizure and frequency as well as seizure severity, were determined using Racine's scale.Moringa oleifera ethanol and hexane extracts produced a delay in the seizure latency in mice and rats; this effect was improved in the presence of the hexane extract containing the active metabolite hexadecanoic acid. The anticonvulsant effects were corroborated in the spectral analysis by the potency of the EEG due to a reduction in the spike frequency and amplitude, as well as in the duration and severity of the seizures. The effects of the hexane extract resembled those observed in the reference antiepileptic drug ethosuximide.Moringa oleifera leaves possess anticonvulsant activities due to the complementary of the non-polar and polar constituents. However, the non-polar constituents appear to exert an important influence via the partial participation of fatty acids, providing evidence of the effects of this plant in epilepsy therapy.

Development of brain synaptosomal uptakes of 3H-norepinephrine and 3H-dopamine in pups whose mothers received ethanol were nearly normal. However, development of synaptosomal uptake of 3H-serotonin was significantly lower than in controls, while uptake of 3H-norepinephrine into synaptic storage vesicles was increased.

Long Sleep (LS) and Short Sleep (SS) mice differ in duration of ethanol-induced sleep time because of differences in brain sensitivity to the depressant effects of alcohols. These lines of mice also differ in their sensitivity to salsolinol, the condensation product of acetaldehyde with dopamine. Some of ethanol's acute effects may be due to salsolinol interactions with catecholamine systems. In the present study, the half-lives of salsolinol were found to be 12.8 min (LS) and 12.3 min (SS). Salsolinol administration resulted in a decrease in brain norepinephrine content in LS but not SS mice. Dopamine levels were not altered by salsolinol. Ethanol or salsolinol, in vitro, inhibited dopamine uptake by striatal synaptosomes. The IC50 values for ethanol were 491 mM (LS) and 514 mM (SS), and for salsolinol, 300 microM (SS). Thus, the mouse line which is most sensitive to the behavioral effects of salsolinol is also most sensitive to salsolinol's effects on norepinephrine levels and inhibition of dopamine uptake. However, much higher concentrations are required to alter dopamine uptake in vitro than are required to alter behavior in vivo.

Both marijuana and alcohol have effects on sleep which can be clinically important if either drug is used heavily. A number of polygraphic studies of both drugs' effect on sleep demonstrate that both are rapid eye movement (REM) sleep suppressors and that both effect the REM sleep deprivation response for days after the acute effects have ceased. Marijuana also increases slow wave sleep compared to alcohol which decreases it. The studies reviewed indicate that marijuana, like alcohol, has persisting effects on neuronal activity and presumably on its underlying neurochemical regulation. Also, the studies suggest that caution should be employed in advising the public about the use of marijuana.