Brain research bulletin
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Sleep is regulated by the interaction of a homeostatic (Process S) and a circadian component. The duration of prior wakefulness is the main factor influencing subsequent sleep duration and its intensity. We investigated in the rat whether the sleep-wake history before sleep deprivation (SD) contributes to the effects of sleep loss incurred during the SD. ⋯ The time constant of the exponential monotonic decay (Td) was higher for the 0.75-1.0 Hz bin compared to all remaining frequency bins of the SWA band, reflecting a slower process determining the slow EEG component during sleep. The data show that the homeostatic response after SD, consisting of increased sleep intensity and sleep consolidation is determined by a combination of SD and the preceding vigilance-state history. The slower dynamics of low frequency delta power compared to fast delta frequencies point to heterogeneity within the traditionally defined SWA band.
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Brain research bulletin · Sep 2007
Novel diastereomeric opioid tetrapeptides exhibit differing pharmacological activity profiles.
A novel opioid peptide antagonist analogue, [3H]Dmt-Tic-(2S,3R)betaMePhe-Phe, derived from the potent, delta-receptor selective TIPP tetrapeptide (Tyr-Tic-Phe-Phe) series was synthesized and radiolabeled by catalytic tritiation of its iodinated precursor peptide. The purified radioprobe exhibited a specific activity of 2.15 TBq/mmol (58 Ci/mmol). The novelty of this compound is that it contains structurally modified tyrosine residue (2',6'-dimethyltyrosine, Dmt1) replacing tyrosine (Tyr1) at the N-terminus, and beta-methyl substituted phenylalanine (betaMePhe3) at the third position. ⋯ In the functional tests, the (2S,3R) and (2R,3S) peptides exhibited partial agonist behaviour by weakly stimulating regulatory G-proteins in CHO cell membranes transfected with different receptors. Both isomers were quite weak partial agonists at the delta-receptor and reasonable partial agonists at the mu-receptor, with a prevalence of (2S,3R) over (2R,3S) for the mu-receptor. Consistent with these observations both stereomers competitively inhibited the stimulation of [35S]GTPgammaS binding induced by the prototype delta-agonist peptide (pClPhe4)-DPDPE in delta(m) CHO cell membranes, and still the (2S,3R) compound exerted more potent delta-antagonist effect. [3H]Dmt-Tic-(2S,3R)betaMePhe-Phe represents a high affinity new radioligand and also constitute further example of the influence of beta-methyl substitution on the potency and selectivity of TIPP analogues, thus becoming a valuable biochemical and pharmacological tool in opioid research.
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Brain research bulletin · Jul 2007
Suppression by intrathecal BmK IT2 on rat spontaneous pain behaviors and spinal c-Fos expression induced by formalin.
The central anti-nociception of BmK IT2, a sodium channel modulator from scorpion Buthus martensi Karsh (BmK) was investigated in this study. It was found that the formalin-induced rat spontaneous flinches and spinal c-Fos expression could be significantly suppressed by intrathecal BmK IT2 pre- or post-formalin injection in a dose-dependent manner. ⋯ In addition, the suppression by intrathecal BmK IT2 on formalin-induced c-Fos expression in superficial laminae was more significant than that in deeper laminae. These results indicate that BmK IT2 can induce central anti-nociceptive response and might thus be a valuable molecular tool for the understanding of pain mechanisms.
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Brain research bulletin · Jul 2007
GABAergic mechanisms of the lateral parabrachial nucleus on sodium appetite.
GABAergic activation in the lateral parabrachial nucleus (LPBN) induces sodium and water intake in satiated and normovolemic rats. In the present study we investigated the effects of GABAA receptor activation in the LPBN on 0.3M NaCl, water, 2% sucrose and food intake in rats submitted to sodium depletion (treatment with the diuretic furosemide subcutaneously+sodium deficient food for 24h), 24h food deprivation or 24 h water deprivation. Male Holtzman rats with bilateral stainless steel cannulas implanted into the LPBN were used. ⋯ Muscimol into the LPBN also reduced food deprivation-induced food intake in the first 30 min of test (1.7+/-0.6g versus saline: 4.1+/-0.6g), without changing water deprivation-induced water intake or 2% sucrose intake in sodium depleted rats. Therefore, although GABAA receptors in the LPBN are not tonically involved in the control of sodium depletion-induced sodium intake, GABAA receptor activation in the LPBN produces an early inhibition and a late facilitation of sodium depletion-induced sodium intake. GABAA activation in the LPBN also inhibits food intake, while it consistently increases only sodium intake and not water, food or sucrose intake.
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Brain research bulletin · May 2007
Randomized Controlled Trial Clinical TrialEffects of NMDA receptor antagonist memantine on mismatch negativity.
Mismatch negativity (MMN) and its magnetic counterpart (MMNm) have been shown to be altered in patients with various psychiatric and neurological disorders, e.g. Alzheimer's disease and schizophrenia, indicating deficits in involuntary attention. N-Methyl-D-aspartate (NMDA) receptor-mediated glutamate dysfunction is suggested to underlie these deficits. ⋯ No changes in amplitude or latency were observed for P1 and N1 peaks. These results indicate that memantine affects involuntary attention without otherwise changing auditory processing of the stimuli. As memantine-induced changes in MMN were detected only in EEG, we suggest that the effect is mostly related to the frontal cortex.