Enhanced corticobulbar excitability in chronic smokers during visual exposure to cigarette smoking cues

Background

Neuroimaging studies of chronic smokers report altered activity of several neural regions involved in the processing of rewarding outcomes. Neuroanatomical evidence suggests that these regions are directly connected to the tongue muscle through the corticobulbar pathways. Accordingly, we examined whether corticobulbar excitability might be considered a somatic marker for nicotine craving.

Methods

We compared motor-evoked potential (MEP) amplitudes recorded from the tongue and the extensor carpi radialis (control muscle) of chronic smokers under drug withdrawal and intake conditions as well as a nonsmoker group. All participants were tested during passive exposure to pictures showing a smoking cue or a meaningless stimulus. In the intake condition, chronic smokers were asked to smoke a real cigarette (CSn: group 1) or a placebo (CSp: group 2).

Results

Results show that MEP amplitudes recorded from the tongues of participants in the CSn and CSp groups under the withdrawal condition were selectively enhanced during exposure to a smoking cue. However, this effect on tongue MEP amplitudes disappeared in the intake condition for both the CSn and CSp groups.

Limitations

Limitations include the fact that the study was conducted in 2 different laboratories, the small sample size, the absence of data on chronic smoker craving strength and the different tastes of the real and placebo cigarettes.

Conclusion

These results suggest that, in chronic smokers, tongue muscle MEP amplitudes are sensitive to neural processes active under the physiological status of nicotine craving. This finding implicates a possible functional link between neural excitability of the corticobulbar pathway and the reward system in chronic smokers.     

Attending to the thalamus: inhibition of return and nasal-temporal asymmetry in the pulvinar

Inhibition of return (IOR) is a mechanism whereby the attentional system favors novel locations by inhibiting already scanned ones. An important question is what the neural structures are involved. Recently, we studied a patient with damage to the superior colliculus (SC) and concluded that the SC generates IOR. However, it is possible that IOR is generated beyond the colliculus, for example, by the pulvinar. In this paper we tested three patients with unilateral damage to the pulvinar and demonstrated that the pulvinar is not necessary for IOR generation, providing additional support to the suggestion that the SC generates IOR. In addition, since we used monocular presentation, we were able to furnish behavioral evidence for nasal-temporal asymmetrical representation of visual input in the pulvinar.     

Genetic deletion of the norepinephrine transporter decreases vulnerability to seizures

Norepinephrine (NE) has been reported to modulate neuronal excitability and act as endogenous anticonvulsant. In the present study we used NE transporter knock-out mice (NET-KO), which are characterized by high levels of extracellular NE, to investigate the role of endogenous NE in seizure susceptibility. Seizure thresholds for cocaine (i.p.), pentylenetetrazol (i.v.) and kainic acid (i.v.) were compared in NET-KO, heterozygous (NET-HT) and wild type (NET-WT) female mice. The dose-response curve for cocaine-induced convulsions was significantly shifted to the right in NET-KO mice, indicating higher seizure thresholds. The threshold doses of pentylenetetrazol that induced clonic and tonic seizures were also significantly higher in NET-KO when compared to NET-WT mice. Similarly, NET-KO mice displayed higher resistance to convulsions engendered by kainic acid. For all drugs tested, the response of NET-HT mice was always intermediate. These data provide further support for a role of endogenous NE in the control of seizure susceptibility.     

Heme oxygenase overexpression attenuates glucose-mediated oxidative stress in quiescent cell phase: linking heme to hyperglycemia complications

Heme oxygenase (HO-1) is a stress protein, which has been suggested to participate in defense mechanisms against glucose induced oxidative injury. The purpose of this study was to examine the role of human HO-1 in attenuating glucose-mediated oxidative stress. We investigated the effect of high ambient glucose (15, 33 and 66 mM) on HO-1 gene expression in endothelial cells grown in a serum deprived media compared to the effect of glucose on exponentially grown cells (10% FBS). High glucose at 15 and 33 mM caused significant inhibition of HO-1 protein and activity in G0/G1 and in cells exponentially grown. Glucose concentration at 66 mM caused a significant increase in HO-1. Addition of heme (10 microM) increased HO-1 protein and bilirubin formation in G0/G1, in a time dependent manner peaking at 16 h. Glucose attenuated heme mediated increase in HO-1 proteins. RT-PCR demonstrated that glucose decreased the levels of HO-1 mRNA in both G0/G1 or cells grown in 10% FBS. The rate of HO-1 induction in response to heme was several fold higher in serum-starved cells compared to cells cultured in 10% FBS. Cells exposed to high glucose for up to 24 h had a significant increase in cellular heme and potentiated heme-mediated increase in generation of superoxide anion and 8-epi-isoprostane PGF(2alpha). HO-1 gene transduction prevented glucose-mediated elevation of 8-epi-isoprostane PGF(2alpha). These results imply that expression of HO-1 in G0/G1 cells may be a key player in decreasing cellular heme, associated with increased generation of bilirubin, and in attenuating glucose mediated oxidative stress.     

Relationships between total and unbound propofol in plasma and CSF during continuous drug infusion

BACKGROUND: Propofol is one of the most frequently applied intravenous anesthetics. Although it has been used for a long period, its pharmacokinetics, especially central nervous system pharmacokinetics, are not fully recognized. OBJECTIVE: Investigation of the relationships between total propofol concentration in blood, total propofol concentration in cerebrospinal fluid (CSF), free propofol concentration in blood, and free anesthetic concentration in CSF in patients undergoing elective neurosurgery and anesthetized with propofol. METHODS: Eleven patients scheduled for elective intracranial procedures were studied. Propofol was applied in the form of target control infusion. During anesthesia, fractional doses of fentanyl and cisatracurium were administered as necessary. After tracheal intubation the lungs were ventilated to achieve normocapnia with an oxygen-air mixture (Fi O2 = 0.33). CSF and blood were taken at the moment of intraventricular drainage application. RESULTS: The unbound propofol concentration in plasma is 1.12% (SD 0.61%; SEM 0.18%) of the total concentration in plasma, and the free propofol concentration in plasma is 71.6% (SD 61.0%; SEM 18.4%) of the total CSF propofol concentration. The free anesthetic concentration in CSF is 30.9% (SD 15.7%; SEM 4.7%) of the total CSF propofol concentration, and 61.8% (SD 34.9%; SEM 10.5%) of the free propofol concentration in plasma. CONCLUSION: The relationship between unbound drug concentrations in plasma and in CSF determined in this study leads to the postulate that propofol is transported from blood to CSF by passive diffusion.