Effects of acupuncture on vasopressin-induced emesis in conscious dogs

Although acupuncture has a significant clinical benefit, the mechanism of acupuncture remains unclear. Vasopressin, a posterior pituitary hormone, is involved in nausea and vomiting in humans and dogs. To investigate the antiemetic effects of acupuncture on vasopressin-induced emesis, gastroduodenal motor activity and the frequency of retching and vomiting were simultaneously recorded in conscious dogs. In seven dogs, four force transducers were implanted on the serosal surfaces of the gastric body, antrum, pylorus, and duodenum. Gastroduodenal motility was continuously monitored throughout the experiment. Vasopressin was intravenously infused at a dose of 0.1 U x kg(-1) x min(-1) for 20 min. Electroacupuncture (EA, 1-30 Hz) at pericardium-6 (PC6), bladder-21 (BL21), or stomach-36 (ST36) was performed before, during, and after the vasopressin infusion. To investigate whether the opioid pathway is involved in EA-induced antiemetic effects, naloxone (a central and peripheral opioid receptor antagonist) or naloxone methiodide (a peripheral opioid receptor antagonist) was administered before, during, and after EA and vasopressin infusion. Intravenous infusion of vasopressin induced retching and vomiting in all dogs tested. Retrograde peristaltic contractions occurred before the onset of retching and vomiting. EA (10 Hz) at PC6 significantly reduced the number of episodes of retching and vomiting. EA at PC6 also suppressed retrograde peristaltic contractions. In contrast, EA at BL21 or ST36 had no antiemetic effects. The antiemetic effect of EA was abolished by pretreatment with naloxone but not naloxone methiodide. It is suggested that the antiemetic effect of acupuncture is mediated via the central opioid pathway.     

Coarse-grained simulation studies of peptide-induced pore formation

We investigate the interactions between lipid bilayers and amphiphilic peptides using a solvent-free coarse-grained simulation technique. In our model, each lipid is represented by one hydrophilic and three hydrophobic beads. The amphiphilic peptide is modeled as a hydrophobic-hydrophilic cylinder with hydrophilic caps. We find that with increasing peptide-lipid attraction the preferred state of the peptide changes from desorbed, to adsorbed, to inserted. A single peptide with weak attraction binds on the bilayer surface, while one with strong attraction spontaneously inserts into the bilayer. We show how several peptides, which individually bind only to the bilayer surface, cooperatively insert. Furthermore, hydrophilic strips along the peptide cylinder induce the formation of multipeptide pores, whose size and morphology depend on the peptides’ overall hydrophilicity, the distribution of hydrophilic residues, and the peptide-peptide interactions. Strongly hydrophilic peptides insert less readily, but prove to be more destructive to bilayer integrity.     

Behavioral and electrophysiological patterns of wakefulness-sleep states in a lizard.

Four individuals of the lizard Ctenosaura pectinata were chronically implanted for electroencephalographic (EEG), electromyographic (EMG) and electro-oculographic (EOG) recordings. Four different vigilance states were observed throughout the nyctohemeral cycle. These states were: Active wakefulness (Aw), quiet wakefulness (Qw), quiet sleep (Qs) and active sleep (As). Each state displayed its own behavioral and electrophysiological characteristics. EEG waves were similar during Aw and Qw but they diminished in amplitude and frequency when passing from these states to Qs, and both parameters increased during As. Muscular activity was intense in Aw, it decreased during Qw and almost disappeared during Qs. This activity reappeared in a phasic way during As, coinciding with generalized motor manifestations. Ocular activity was intense during Aw but minimal during Qw, it disappeared in Qs and was present intermittently in As. Aw, Qw, Qs and As occupied 5.9%, 25.7%, 67.7% and 0.6% of the 24 hr period, respectively. The frequency and duration of As episodes showed great inter-animal variability and the mean duration was of 12.9 sec. Stimuli reaction threshold was highest during sleep. In conclusion, the lizard Ctenosaura pectinata exhibit two sleep phases (Qs and As) that may be assimilated to slow wave sleep (SWS) and paradoxical sleep (PS) of birds and mammals.     

Behavioral and electrophysiological indices of negative affect predict cocaine self-administration

The motivation to seek cocaine comes in part from a dysregulation of reward processing manifested in dysphoria, or affective withdrawal. Learning is a critical aspect of drug abuse; however, it remains unclear whether drug-associated cues can elicit the emotional withdrawal symptoms that promote cocaine use. Here we report that a cocaine-associated taste cue elicited a conditioned aversive state that was behaviorally and neurophysiologically quantifiable and predicted subsequent cocaine self-administration behavior. Specifically, brief intraoral infusions of a cocaine-predictive flavored saccharin solution elicited aversive orofacial responses that predicted early-session cocaine taking in rats. The expression of aversive taste reactivity also was associated with a shift in the predominant pattern of electrophysiological activity of nucleus accumbens (NAc) neurons from inhibitory to excitatory. The dynamic nature of this conditioned switch in affect and the neural code reveals a mechanism by which cues may exert control over drug self-administration.     

Behavioral and electrophysiological changes induced by acetyl-L-carnitine in aged freely-moving rats

In chronically-implanted, drug-free, behaving aged Fischer rats, intracerebroventricularly (i.c.v.) and intraperitoneally (i.p.) acetyl-L-carnitine (ALCAR) injections powerfully enhanced motor behavior and head movements aimed at attention and exploratory activity. This effect was dose-dependent and associated with the abolition or substantial reduction of the incidence and duration of the spontaneous EEG generalized hypersynchronous patterns termed High Voltage Spindle (HVS), with an increase in EEG monitored theta activity. The results suggest that ALCAR may stimulate the motivational system and disrupt the hypersynchronous processes by inhibiting the GABAergic thalamic reticular neurons and/or activating the brain stem cholinergic reticular system (pedunculo pontine tegmental, PPT and laterodorsal tegmental, LDT nuclei).     

T cell studies in a peptide-induced model of systemic lupus erythematosus

We have previously reported that immunization with a peptide mimetope of dsDNA on a branched polylysine backbone (DWEYSVWLSN-MAP) induces a systemic lupus erythematosus-like syndrome in the nonautoimmune BALB/c mouse strain. To understand the mechanism underlying this breakdown in self tolerance, we examined the role of T cells in the response. Our results show that the anti-foreign and anti-self response induced by immunization is T cell dependent and is mediated by I-E(d)-restricted CD4(+) T cells of the Th1 subset. In addition, generation of the critical T cell epitope requires processing by APCs and depends on the presence of both DWEYSVWLSN and the MAP backbone. The breakdown in self tolerance does not occur through cross-reactivity between the T cell epitope of DWEYSVWLSN-MAP and epitopes derived from nuclear Ags. In this induced-model of SLE, therefore, autoreactivity results from the activation of T cells specific for foreign Ag and of cross-reactive anti-foreign, anti-self B cells. Despite the fact that tissue injury is mediated by Ab, the critical initiating T cell response is Th1.     

Behavioral and electrophysiological responses to NaCl in young and old Fischer-344 rats

This study compared both behavioral and electrophysiologicalresponses to NaCl in young and old Fischer-344 rats. These comparisonswere made in the same individuals. Preference for NaCl solutionsversus water was assessed using two-bottle preference tests.The integrated response of the chorda tympani nerve to NaClwas recorded. NaCl neural-response magnitude and correspondingbehavioral sensitivity appear to decrease with age in the Fischer-344rat at concentrations > 0.15 M and neural-response magnitudesincrease at lower concentrations.     

Behavioral and electrophysiological studies on the sexually biased synergism between oligosaccharides and phospholipids in gustatory perception of nuptial secretion by the German cockroach

Females of Blattella germanica feed compulsively on a nuptial secretion from the male's eighth tergal gland (TG-8) during courtship. Using TG-8 extract and its essential ingredients, maltotriose (MT) and 1,2-dioleoylphosphatidylcholine (PC), we investigated the perception of the secretion by gustatory sensilla in both sexes. Female-biased chemosensitivity was found in the feeding responses to the TG-8 extract. The TG-8 extract induced specific impulses in four functionally different receptor cells: the sugar, salt and other two types of receptor cells in a single gustatory sensillum on the paraglossae in both sexes. The impulse frequencies of the sugar receptor cell and a receptor cell of unknown type were significantly higher in females than those in males. There were no sexual differences in the behavioral and electrophysiological responses to MT alone; no responses were elicited by PC. However, a mixture of MT and PC elicited the behavioral responses more strongly than MT in females. The impulse frequency of sugar receptor cells toward the mixture of MT and PC also increased in females but not in males. These results suggest that the synergistic effect of PC on ‘sweetness’ of MT in the female cockroach contributes to her compulsive nuptial feeding. The female-biased gustatory sensitivity seems to ensure successful coupling during the nuptial feeding.     

Behavioral and electrophysiological analysis of general anesthesia in 3 background strains of Drosophila melanogaster

General anesthetics achieve behavioral unresponsiveness via a mechanism that is incompletely understood. The study of genetic model systems such as the fruit fly Drosophila melanogaster is crucial to advancing our understanding of how anesthetic drugs render animals unresponsive. Previous studies have shown that wild-type control strains differ significantly in their sensitivity to general anesthetics, which potentially introduces confounding factors for comparing genetic mutations placed on these wild-type backgrounds. Here, we examined a variety of behavioral and electrophysiological endpoints in Drosophila, in both adult and larval animals. We characterized these endpoints in 3 commonly used fly strains: wild-type Canton Special (CS), and 2 commonly used white-eyed strains, isoCJ1 and w¹¹¹⁸. We found that CS and isoCJ1 show remarkably similar sensitivity to isoflurane across a variety of behavioral and electrophysiological endpoints. In contrast, w¹¹¹⁸ is resistant to isoflurane compared to the other 2 strains at both the adult and larval stages. This resistance is however not reflected at the level of neurotransmitter release at the larval neuromuscular junction (NMJ). This suggests that the w¹¹¹⁸ strain harbors another mutation that produces isoflurane resistance, by acting on an arousal pathway that is most likely preserved between larval and adult brains. This mutation probably also affects sleep, as marked differences between isoCJ1 and w¹¹¹⁸ have also recently been found for behavioral responsiveness and sleep intensity measures.     

Behavioral, electrophysiologic and vegetative correlates of self stimulation in dogs]

Summary electrical activity of different brain structures (chiefly the hippocampal theta-rhythm) and cardiac and respiratory rhythms were recorded during self-stimulation (SS) in dogs. Emotional-motivational excitation in dogs, preceding SS, is attended with a moderate increase in theta-activity in the hippocampus. The SS period is characterized by desynchronization of the electrical activity, the appearance of high-frequency rhythmics and diminished theta-rhythm. After withdrawal of the pedal, hypersynchronization of the theta-rhythm sets in in most of the structures studied. SS is accompanied by considerable shifts of the cardiac and respiratory rhythms. The dynamics of behavioral, electrophysiological and vegetative shifts during SS in dogs points to a successive involvment of the brain mechanisms of search, positive reinforcement and emotional-negative interruption of the pedal pressing series. Complex interaction of the three mechanisms underlies the external phenomenology of the SS instrumental conditioned reflex.     

Synthesis and electrophysiological studies of a novel epibatidine analogue

The new epibatidine analogue exo-2-(2-pyridyl)-7-azabicyclo[2.2.1]heptane (2PABH) was synthesised. Separation of enantiomers was performed on chiral HPLC chromatography in polar-organic phase mode at 0 degree C. Enantiomeric purity was greater than 99.8%ee for the (-)- and 90.5%ee for the (+)-enantiomer respectively. Optical rotation was determined to be [alpha]23D = +/- 13 degrees. Electrophysiological studies of 2PABH were carried out on alpha 4 beta 2, alpha 3 beta 4 and alpha 7 nAChR subtypes cloned from rat and reconstituted in Xenopus oocytes. Both enantiomers could not significantly activate the heteromeric subtypes. The homomeric alpha 7 nAChR displays a high sensitivity only towards (-)-2PABH. The EC50 for (-)-2PABH and ACh were determined (32.5 +/- 9.5 microM, 137.3 +/- 16.5 microM). (-)-2PABH was shown to be a partial agonist (80% of ACh). Thus the efficacy of 2PABH differs markedly from that of epibatidine. The intramolecular N-N-distance and the spatial pyridine nitrogen orientation play a central role in nAChR recognition.     

Behavioral and electrophysiological taste responses change after brief or prolonged dietary sodium deprivation

Dietary Na+ deprivation elicits a hormonal response to promote sodium conservation and a behavioral response to increase sodium ingestion. It has generally been accepted that the former occurs within 24 h after sodium deprivation, while the latter is delayed and may not appear until as much as 10 days later. Na+ deprivation of similar duration also decreases the sensitivity of the chorda tympani nerve (CT) to NaCl, suggesting that changes in CT responses are necessary for increased NaCl intake. However, previous work from our laboratory showed that licking responses to NaCl solutions increase after only 2 days of Na+ deprivation, suggesting rapidly occurring changes in response to NaCl taste. The present experiments examined the effects of 2 days of dietary Na+ deprivation on CT responses to NaCl and patterns of NaCl consumption and found that Na+-deficient rats licked significantly more during the first NaCl intake bout compared with control rats. CT responses to NaCl were reduced at all concentrations after brief Na+ deprivation compared with Na+-replete control rats and did not decrease further with prolonged (10 days) dietary Na+ deficiency. Moreover, amiloride, which suppressed CT responses to NaCl by approximately 30% in control rats, had virtually no effect on CT responses in Na+-deprived rats. Thus, 2 days of Na+ deprivation is sufficient to alter patterns of ingestion of concentrated NaCl and to reduce gustatory responses to NaCl. Furthermore, changes in gustatory responses to NaCl during dietary Na+ deprivation may involve the amiloride-sensitive component of the CT.