Photobiomodulation Increases Viability in Full-Thickness Grafts in Rats Submitted to Nicotine.

BACKGROUND AND OBJECTIVES: Photobiomodulation (PBM) therapy with 830 nm wavelength or 660 wavelength to compare the effects with parameters of 30 mW, 0.028 cm2 , 9.34 seconds, and 3.64 J on the total integration of total skin grafts in rats submitted to nicotine. STUDY DESIGN/MATERIALS AND METHODS: Sixty male Wistar rats were divided in six groups: Sham-skin-grafting surgery; 830 nm-skin-grafting followed by 830 nm irradiation; 660 nm-skin grafting followed by 660 nm irradiation; Nicotine-subjected to subcutaneous nicotine injection (2 mg/kg twice a day for 4 weeks), followed by skin grafting; Group Nicotine/830 nm-similar to Group Nicotine, followed by 830 nm irradiation; Group Nicotine/660 nm-similar to Group Nicotine, followed by 660 nm irradiation. The percentage contraction of the grafting tissue was evaluated through ImageJ®. The thickness of the epidermis, inflammatory infiltrates, and the space between the implanted tissue and receptor bed were determined by histology; and the expression of vascular growth factor and blood vessel density (factor VIII) were evaluated by immunohistochemistry. RESULTS: The PBM at both wavelengths promoted a facilitating effect on the integration of the skin graft under nicotine and had a more significant effect on the thickness of the epidermis and expression of angiogenesis without nicotine at a wavelength of 830 nm. Different wavelengths influence responses related to the viability of cutaneous grafts in rats submitted to nicotine. CONCLUSIONS: The PBM with 830 nm and 660 nm promoted beneficial results in skin grafts submitted to the deleterious action of nicotine. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.

Central nicotine induces browning through hypothalamic κ opioid receptor.

Increased body weight is a major factor that interferes with smoking cessation. Nicotine, the main bioactive compound in tobacco, has been demonstrated to have an impact on energy balance, since it affects both feeding and energy expenditure at the central level. Among the central actions of nicotine on body weight, much attention has been focused on its effect on brown adipose tissue (BAT) thermogenesis, though its effect on browning of white adipose tissue (WAT) is unclear. Here, we show that nicotine induces the browning of WAT through a central mechanism and that this effect is dependent on the κ opioid receptor (KOR), specifically in the lateral hypothalamic area (LHA). Consistent with these findings, smokers show higher levels of uncoupling protein 1 (UCP1) expression in WAT, which correlates with smoking status. These data demonstrate that central nicotine-induced modulation of WAT browning may be a target against human obesity.

Differential associations of combined vs. isolated cannabis and nicotine on brain resting state networks.

Concomitant cannabis and nicotine use is more prevalent than cannabis use alone; however, to date, most of the literature has focused on associations of isolated cannabis and nicotine use limiting the generalizability of existing research. To determine differential associations of concomitant use of cannabis and nicotine, isolated cannabis use and isolated nicotine use on brain network connectivity, we examined systems-level neural functioning via independent components analysis (ICA) on resting state networks (RSNs) in cannabis users (CAN, n = 53), nicotine users (NIC, n = 28), concomitant nicotine and cannabis users (NIC + CAN, n = 26), and non-users (CTRL, n = 30). Our results indicated that the CTRL group and NIC + CAN users had the greatest functional connectivity relative to CAN users and NIC users in 12 RSNs: anterior default mode network (DMN), posterior DMN, left frontal parietal network, lingual gyrus, salience network, right frontal parietal network, higher visual network, insular cortex, cuneus/precuneus, posterior cingulate gyrus/middle temporal gyrus, dorsal attention network, and basal ganglia network. Post hoc tests showed no significant differences between (1) CTRL and NIC + CAN and (2) NIC and CAN users. These findings of differential associations of isolated vs. combined nicotine and cannabis use demonstrate an interaction between cannabis and nicotine use on RSNs. These unique and combined mechanisms through which cannabis and nicotine influence cortical network functional connectivity are important to consider when evaluating the neurobiological pathways associated with cannabis and nicotine use.

A deficiency of the link protein Bral2 affects the size of the extracellular space in the thalamus of aged mice.

Bral2 is a link protein stabilizing the binding between lecticans and hyaluronan in perineuronal nets and axonal coats (ACs) in specific brain regions. Using the real-time iontophoretic method and diffusion-weighted magnetic resonance, we determined the extracellular space (ECS) volume fraction (α), tortuosity (λ), and apparent diffusion coefficient of water (ADCW ) in the thalamic ventral posteromedial nucleus (VPM) and sensorimotor cortex of young adult (3-6 months) and aged (14-20 months) Bral2-deficient (Bral2-/- ) mice and age-matched wild-type (wt) controls. The results were correlated with an analysis of extracellular matrix composition. In the cortex, no changes between wt and Bral2-/- were detected, either in the young or aged mice. In the VPM of aged but not in young Bral2-/- mice, we observed a significant decrease in α and ADCW in comparison with age-matched controls. Bral2 deficiency led to a reduction of both aggrecan- and brevican-associated perineuronal nets and a complete disruption of brevican-based ACs in young as well as aged VPM. Our data suggest that aging is a critical point that reveals the effect of Bral2 deficiency on VPM diffusion. This effect is probably mediated through the enhanced age-related damage of neurons lacking protective ACs, or the exhausting of compensatory mechanisms maintaining unchanged diffusion parameters in young Bral2-/- animals. A decreased ECS volume in aged Bral2-/- mice may influence the diffusion of neuroactive substances, and thus extrasynaptic and also indirectly synaptic transmission in this important nucleus of the somatosensory pathway.

[EXPERIMENTAL STUDY ON EFFECT OF NICOTINE INTAKE ON IMPACT OF BONE MICROSTRUCTURE AND OXIDATIVE STRESS IN RATS].

OBJECTIVE: To evaluate the influence of nicotine intake on bone microstructure, bone biomechanics, and oxidative stress state in rats. METHODS: Thirty-six 6-week-old male Sprague Dawley rats (weight, 160-180 g) were randomly divided into control group, low dose group, and high dose group, 12 rats each group. The rats in high dose group and low dose group were given respectively 6.0 mg/kg and 0.4 mg/kg nicotine gavage intervention for 12 months; no intervention was made in the control group. The survival of rats was observed during experiment, and the weight of rats was measured every month. At 12 months after modeling, the L1 vertebral body was harvested to measure the bone mineral density (BMD), bone volume fraction (BVF), trabecular thickness (TT), trabecular number (TN), and trabecular spacing (TS) by Micro-CT three-dimensional reconstruction; the left femur was harvested for biomechanical tests of maximal load, stiffness, and the maximal fracture energy; and arterial blood was extracted to measure the malonyldialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and cotinine. RESULTS: During the experiment, two rats and one rat were added in the high dose group and the low dose group because of death, and no death in the control group. The body weight of the rats in the high and low dose groups gradually decreased with time when compared with one in the control group, and significant difference was found between two dose groups and the control group at 8-12 months (P<0.05); the body weight of the high dose group was significantly lower than that of the low dose group at 11 and 12 months (P<0.05). At 12 months after modeling, BMD, BVF, TT, and TN were significantly lower in the high dose group than the control group and the low dose group, but TS was significantly increased (P<0.05). Difference in BVF, TN, and TS was significant between the low dose group and the control group (P<0.05). The maximal load, stiffness, and maximal fracture energy of femoral shaft were significantly lower in the high dose group than the control group and the low dose group, and in the low dose group than the control group (P<0.05). Compared with the control group, the levels of cotinine and MDA were significantly increased, and the levels of CAT and SOD were significantly decreased in the high and low dose groups (P<0.05), and there were significant differences between the high and low dose groups (P<0.05). CONCLUSIONS: Nicotine intake can cause micro-structural changes of the bone, decreased bone mechanical properties, and imbalance of oxidation-antioxidant levels in rats. High-dose nicotine intake may be one of the causes of osteoporosis.

Chronic nicotine treatment enhances vascular smooth muscle relaxation in rats.

AIM: To investigate the effect of chronic nicotine treatment on vascular function and to identify the underlying mechanisms. METHODS: Adult rats were treated with nicotine (3 mg·kg(-1)·d(-1), sc) for 6 weeks. After the rats were sacrificed, aortic rings were prepared for detecting vascular reactivity, and thoracic aorta and periaortic fat samples were collected for histological and molecular biology studies. RESULTS: Chronic nicotine treatment significantly reduced periaortic fat, and specifically enhanced smooth muscle relaxation without altering the aortic adventitial fat and endothelium function. Pretreatment with the soluble guanylyl cyclase inhibitor ODQ (3 µmol/L) or PKG inhibitor Rp-8-Br-PET-cGMP (30 µmol/L) abolished the nicotine-induced enhancement of smooth muscle relaxation, whereas the cGMP analogue 8-Br-cGMP could mimic the nicotine-induced enhancement of smooth muscle relaxation. However, the chronic nicotine treatment did not alter PKG protein expression and activity in aortic media. CONCLUSION: Chronic nicotine treatment enhances vascular smooth muscle relaxation of rats via activation of PKG pathway.

Dose-dependent effects of nicotine on proliferation and differentiation of human bone marrow stromal cells and the antagonistic action of vitamin C.

A range of biological and molecular effects caused by nicotine are considered to effect bone metabolism. Vitamin C functions as a biological antioxidant. This study was to evaluate the in vitro effects of nicotine on human bone marrow stromal cells and whether Vitamin C supplementation show the antagonism action to high concentration nicotine. We used CCK-8, alkaline phosphatase (ALP) activity assay, Von Kossa staining, real-time polymerase chain reaction and Western Blot to evaluate the proliferation and osteogenic differentiation. The results indicated that the proliferation of BMSCs increased at the concentration of 50, 100 ng/ml, got inhibited at 1,000 ng/ml. When Vitamin C was added, the OD for proliferation increased. For ALP staining, we found that BMSCs treated with 50 and 100 ng/ml nicotine showed a higher activity compared with the control, and decreased at the 1,000 ng/ml. Bone morphogenetic protein-2 (BMP-2) expression and the calcium depositions decreased at 100 and 1,000 ng/ml nicotine, while the addition of Vitamin C reversed the down regulation. By real-time PCR, we detected that the mRNA expression of collagen type I (COL-I) and ALP were also increased in 50 and 100 ng/ml nicotine groups (P < 0.05), while reduced at 1,000 ng/ml (P < 0.05). When it came to osteocalcin (OCN), the changes were similar. Taken all together, it is found that nicotine has a two-phase effect on human BMSCs, showing that low level of nicotine could promote the proliferation and osteogenic differentiation while the high level display the opposite effect. Vitamin C could antagonize the inhibitory effect of higher concentration of nicotine partly.

Differential sensitivity to nicotine among hypothalamic magnocellular neurons.

OBJECTIVES: The magnocellular neurons in the hypothalamic paraventricular (PVN) and supraoptic nuclei (SON) either contain vasopressin or oxytocin. Even though both hormones are released after systemic administration of nicotine, the mechanism through which the two populations of neurons are activated is not known. This study was carried out in the rat to investigate the effect of increasing doses of nicotine on subsets of magnocellular neurons containing either oxytocin or vasopressin. METHODS: The activated neurons were identified by means of Fos immunohistochemistry and the induction of Fos in magnocellular subdivisions was investigated by means of dual-immunohistochemistry. RESULTS: While oxytocinergic neurons were sensitive to systemic administration of 0.5 mg/kg of nicotine, vasopressinergic neurons were not affected at doses up to 1 mg/kg. The vast majority (85%) of oxytocinergic neurons in the PVN was affected by nicotine, whilst only about half of the vasopressinergic neurons were stimulated, and only at maximal doses. Notably, the sensitivity of oxytocinergic neurons to nicotine was found to be different in the PVN and SON, because only about 55% of the SON oxytocinergic neurons co-stored Fos even after the highest dose of nicotine. CONCLUSION: These data show that magnocellular neurons are differentially regulated by nicotine and that their sensitivity is dependent on both their peptidergic phenotype and their location within the hypothalamus. KEYWORDS: acetylcholine, vasopressin, oxytocin, Fos, stress, cell counting.

Prenatal IV nicotine exposure produces a sex difference in sensorimotor gating of the auditory startle reflex in adult rats.

Maternal smoking during pregnancy is associated with auditory processing deficits in children; these effects have been confirmed with animal models of continuous high-dose prenatal nicotine exposure. The present experiments utilized a novel, low-dose, intermittent, intravenous (IV) gestational nicotine exposure model to investigate potential deficits on the preattentive process of sensorimotor gating, as indexed by prepulse inhibition (PPI), in preweanling and adult rat offspring. Pregnant dams received bolus IV injections of nicotine (0.05 mg/kg/injection) 3×/day on gestational days 8-21. Auditory and tactile stimulus modalities were probed with tone and air puff prepulse stimuli, respectively. These prepulse stimuli preceded a 100 dB(A) startle tone by six different interstimulus intervals (ISIs; 0, 8, 40, 80, 120, 4000 ms) to define a curve of response inhibition. The magnitude of PPI increased with age, from 59 to 81% inhibition. Preweanlings (PNDs 14 and 18) and adults (PND 75) gestationally exposed to nicotine exhibited altered startle responding relative to controls, but the nature of the deficit became more localized at later ages. The entire curve of response inhibition in preweanlings exposed to prenatal nicotine (PND 14) was shifted up relative to controls, and notably, did not interact with prepulse stimulus modality, suggesting a generalized increased sensorimotor responsiveness as a function of prenatal nicotine. At PND 18, a shift in the response curve across all ISIs was again noted, but varied as a function of prepulse stimulus modality; the increased sensorimotor responsiveness was specific to the auditory, but not tactile, sensory modality. In adulthood, male and female animals prenatally exposed to nicotine were differentially sensitive to modulation by the ISIs, relative to control male and female animals. Specifically, despite robust PPI, adult females exposed to gestational nicotine were relatively insensitive to changes in ISI from 8 to 120 ms; in contrast, the robust PPI of nicotine-exposed males demonstrated a clear focal point of inhibition at 40 ms. These findings indicate that a low, daily dosing of IV prenatal nicotine produces long-lasting alterations in auditory PPI. An important implication of this research is that "chipping" with smoked-tobacco products during pregnancy may produce enduring changes in sensorimotor processing.

Thalamic microinjection of nicotine reverses sevoflurane-induced loss of righting reflex in the rat.

BACKGROUND: Neuronal nicotinic acetylcholine receptors are both potently inhibited by anesthetics and densely expressed in the thalamus. Brain imaging shows that thalamic activity suppression accompanies anesthetic-induced unconsciousness. Therefore, anesthetic-induced unconsciousness may involve direct antagonism of thalamic nicotinic receptors. The authors test this by separately attempting to block or enhance anesthetic-induced loss of righting in rats using intrathalamic microinjections of nicotine or its antagonist. METHODS: Rats were implanted with a cannula aimed at the thalamus or control locations. A week later, loss of righting was induced using sevoflurane (1.4 +/- 0.2%). A dose-parameter study (n = 35) first identified an optimal intrathalamic nicotine dose associated with arousal. Subsequently, this dose was used to pinpoint the thalamic site mediating the arousal response (n = 107). Finally, sevoflurane righting dose and response specificity were assessed after blocking nicotinic channels with intrathalamic mecamylamine pretreatment (n = 8) before nicotine challenge. RESULTS: Nicotine (150 microg/0.5 microl over 1 min) was the optimal arousal dose, because lower doses (75 microg) were ineffective and higher doses (300 microg) often caused seizures. Nicotine temporarily restored righting and mobility in animals when microinjections involved the central medial thalamus (P < 0.0001, chi-square). Righting occurred despite continued sevoflurane administration. Intrathalamic mecamylamine pretreatment did not lower the sevoflurane dose associated with loss of righting, but prevented the nicotine arousal response. CONCLUSIONS: The reversal of unconsciousness found here with intrathalamic microinfusion of nicotine suggests that suppression of the midline thalamic cholinergic arousal system is part of the mechanism by which anesthetics produce unconsciousness.

Effects of nicotine and vitamin E on glutathione reductase activity in some rat tissues in vivo and in vitro.

Effects of nicotine, and nicotine+vitamin E on glutathione reductase (Glutathione: NADP(+) oxidoreductase, EC 1.8.1.7) activity in the muscle, heart, lungs, testicles, kidney, stomach, brain and liver tissues were investigated in vivo and also in vitro. The groups were: nicotine [0.5 mg/kg/day, intraperitoneal (i.p.)]; nicotine+vitamin E [75 mg/kg/day, intragastric (i.g.)]; and control group (receiving only vehicles). There were eight rats per group and supplementation period was 3 weeks. The results showed that nicotine (0.5 mg/kg, i.p.) inhibited glutathione reductase activity significantly in the liver, lungs, heart, stomach, kidney, and testicles by approximately 61.5%, approximately 65%, approximately 70.5%, approximately 72.5%, approximately 64% and approximately 71.5%, respectively, while it had activated glutathione reductase activity in the brain by approximately 11.8%, and had no effect on the muscle glutathione reductase activity. Vitamin E supplementation prevented this nicotine-induced decrease in glutathione reductase activity in liver, lungs, heart, stomach, and kidney. However, it did not prevent this nicotine-induced decrease in testicles. In vitro studies were also carried out to elucidate the effects of nicotine and vitamin E on glutathione reductase activity. In vitro results correlated well with in vivo experimental results in liver, lungs, heart, stomach, and testicular tissues. These results show that vitamin E administration generally restores the inactivation of glutathione reductase activity due to nicotine administration in various rat tissues in vivo, and also in vitro.

Activation of orexin neurons by acute nicotine.

The hypothalamus is a prominent central site of action of nicotine but the phenotype of nicotine-sensitive neurons in this region has not been fully described. Hypothalamic orexin neurons are important regulators of state-dependent behavior, arousal and feeding. Here, we treated rats with acute nicotine and quantitated Fos expression as a marker of neuronal activation. Nicotine increased the percentage of orexin neurons expressing Fos without a significant effect on non-orexin neurons. This effect was attenuated by the nicotinic antagonists mecamylamine and dihydro-beta-erythroidine, implicating alpha4beta2-containing nicotinic receptors. The orexin system is likely to play an important role in the coordination of physiological and behavioral responses to acute nicotine treatment.

[Behavioral and cognitive therapy to break the smoking habit. Review of the literature]. / Les thérapies comportementales et cognitives dans l'aide à l'arrêt du tabac.

Nicotine addiction is a chronic disease characterized by frequent relapse. Pharmacological and psychological factors are involved and must be specifically addressed in addicts under treatment. Physicians are familiar with pharmacological treatment with nicotine replacement therapy and bupropion, but not with psychological approaches such as behavioral and cognitive therapy. Various techniques have been evaluated during smoking cessation trials: aversive therapy, contracts, social support, stimulus control, relaxation, diet and nicotine fading. Such approaches have been completed with cognitive strategies and therapeutic programs often use motivational interviews, skills training and relapse prevention strategies. This article reviews these techniques and presents the results of a recent meta-analysis evaluating their efficacy. These results confirm the efficacy of behavioral and cognitive therapy in smoking cessation.

Up-regulation of L-type voltage-dependent calcium channels after long term exposure to nicotine in cerebral cortical neurons.

Effects of long term (72-h) exposure to low concentration (0.1 mum) of nicotine on various types of voltage-dependent Ca(2+) channels (VDCCs) and neuronal nicotinic acetylcholine receptors (nnAChRs) were examined using primary cultures of mouse cerebral cortical neurons. High potassium (30 mm KCl)-stimulated (45)Ca(2+) influx into the neurons increased with increasing the duration of nicotine exposure and its concentrations. The maximal increase of the KCl-stimulated (45)Ca(2+) influx was found 24 h after the initiation of exposure and thereafter maintained up to 72 h. This enhancement of KCl-induced (45)Ca(2+) influx after 72-h exposure to 0.1 mum nicotine was completely abolished by concomitant exposure with mecamylamine, an inhibitor for nnAChRs. Only the component of the KCl-induced (45)Ca(2+) influx observed after long term exposure to nicotine, which was sensitive to nifedipine, an inhibitor of L-type VDCCs, was facilitated, while the (45)Ca(2+) influx through P/Q- and N-type VDCCs showed no changes. Moreover, enhanced immunoreactivity against antibody for the alpha(1C) subunit of L-type VDCCs was recognized, whereas no changes in immunoreactivities against antibodies for alpha(1A) and alpha(1B) subunits of other types of VDCCs were noted. In addition, a Western blot analysis showed an increase of immunoreactivities against antibodies for alpha(1D) and alpha(2)/delta(1), and expression of mRNA for L-type VDCC subunit, alpha(1F), was also enhanced, although beta(4) mRNA expression was not changed. Whole cell patch clamp analysis revealed that the increase of the amplitude of Ba(2+) currents was also recognized in the neurons exposed to nicotine, and nicardipine reduced this increased amplitude to the level of the amplitude detected in nontreated neurons with nicardipine. The up-regulation of alpha(4) and beta(2) subunits, but not the alpha(3) subunit of nnAChRs, was also noted after the nicotine exposure when examining by the Western blot analysis. Taken together, these results indicate that the long term exposure of the neurons to a low concentration of nicotine induces both increased (45)Ca(2+) influx through up-regulated L-type VDCCs and nnAChR up-regulation.

Hypothalamic dopamine and serotonin in the regulation of food intake.

Because daily food intake is the product of the size of a meal and the frequency of meals ingested, the characteristic of meal size to meal number during a 24-h light-dark cycle constitutes an identifiable pattern specific to normal states and obesity and that occurs during early cancer anorexia. An understanding of simultaneous changes in meal size and meal number (constituting a change in feeding patterns) as opposed to an understanding of only food intake provides a more insightful dynamic picture reflecting integrated behavior. We have correlated this to simultaneous changes in dopamine and serotonin concentrations and to their postsynaptic receptors, focusing simultaneously on two discrete hypothalamic food-intake-related nuclei, in response to the ingestion of food. The relation between concentrations of dopamine and serotonin limited to the lateral hypothalamic area (LHA) and the ventromedial nucleus (VMN) as they relate to the influence of meal size and meal number during the hyperphagia of obesity and anorexia of cancer as measured in our experiments are discussed. Based on these data, conceptual models are proposed concerning: 1) an "afferent-efferent neurotransmitter unit," with facilitatory or inhibitory neuropeptide properties to generate an appropriate neuroendocrine and neuronal response that ultimately modifies food intake; 2) initiation and termination of a meal, thereby determining the number and size of a meal under normal conditions; and 3) a schema integrating the onset mechanism of cancer anorexia. Nicotine is used as a tool to further explore the relation of meal size to meal number, with a focus on simultaneous changes in dopamine and serotonin concentrations in the LHA and VMN with the onset of acute anorexia of nicotine infusion and acute hyperphagia of nicotine cessation. Data concerning the role of sex-related hormones on dopamine and serotonin with regard to the LHA and VMN in relation to the modulation of food intake are also presented.

Activation of neurons in rat trigeminal subnucleus caudalis by different irritant chemicals applied to oral or ocular mucosa.

To investigate the role of trigeminal subnucleus caudalis in neural mechanisms of irritation, we recorded single-unit responses to application of a variety of irritant chemicals to the tongue or ocular mucosa in thiopental-anesthetized rats. Recordings were made from wide dynamic range (WDR) and nociceptive-specific units in superficial layers of the dorsomedial caudalis (0-3 mm caudal to obex) responsive to mechanical stimulation and noxious heating of the ipsilateral tongue ("tongue" units) and from WDR units in ventrolateral caudalis (0-2 caudal to obex) responsive to mechanical and noxious thermal stimulation of cornea-conjunctiva and frequently also surrounding skin ("cornea-conjunctival" units). The following chemicals were delivered topically (0.1 ml) onto the dorsal anterior tongue or instilled into the ipsilateral eye: capsaicin (0.001-1% = 3.3 x 10(-2) to 3.3 x 10(-5) M), ethanol (15-80%), histamine (0.01-10% = 9 x 10(-1) to 9 x 10(-4) M), mustard oil (allyl-isothiocyanate, 4-100% = 4 x 10(-1) to 10 M), NaCl (0.5-5 M), nicotine (0.01-10% = 6 x 10(-1) to 6 x 10(-4) M), acidified phosphate buffer (pH 1-6), piperine (0.01-1% = 3.5 x 10(-2) to 3.5 x 10(-4) M), serotonin (5-HT; 0.3-3% = 1.4 x 10(-1) to 1.4 x 10(-2) M), and carbonated water. The dose-response relationship and possible tachyphylaxis were tested for each chemical. Of 32 tongue units, 31 responded to one or more, and frequently all, chemicals tested. The population responded to 75.3% of the various chemicals tested (

Cholinergic and noradrenergic modulation of the slow (approximately 0.3 Hz) oscillation in neocortical cells.

1. The pedunculopontine tegmental (PPT) cholinergic nucleus and the locus coeruleus (LC) noradrenergic nucleus were electrically stimulated to investigate their effects on the recently described slow oscillation (approximately 0.3 Hz) of neocortical neurons. Intracellular recordings of slowly oscillating, regular-spiking and intrinsically bursting neurons from cortical association areas 5 and 7 (n = 140) were performed in anesthetized cats. 2. Pulse trains to the PPT nucleus produced the blockage of rhythmic (approximately 0.3 Hz) depolarizing-hyperpolarizing sequences in 79% of tested cortical neurons and transformed this slow cellular rhythm into tonic firing. The latency of the cortical cellular response to PPT stimulation was 1.2 +/- 0.5 (SE) s and its duration was 15.9 +/- 1.9 s. The PPT-elicited suppression of the slow cellular oscillation was accompanied by an activation of the electroencephalogram (EEG) having a similar time course. Fast Fourier transform analyses of EEG activities before and after PPT stimulation showed that the PPT-evoked changes consisted of decreased power of slow rhythms (0-8 Hz) and increased power of fast rhythms (24-33 Hz); these changes were statistically significant. 3. The blockage of the slow cellular oscillation was mainly achieved through the diminution or suppression of the long-lasting hyperpolarizations separating the rhythmic depolarizing envelopes. This effect was observed even when PPT pulse trains disrupted the oscillation without inducing overt depolarization and increased firing rate. The durations of the prolonged hyperpolarizations were measured during a 40-s window (20 s before and 20 s after the PPT pulse train) and were found to decrease from 1.5 +/- 0.2 to 0.7 +/- 0.1 s. The values of the product resulting from the duration (in seconds), the amplitude (in millivolts), and number of such hyperpolarizing events within 20-s periods were 51.5 +/- 5 and 5.1 +/- 1.9 before and after PPT stimulation, respectively. 4. The PPT effect was suppressed by systemic administration of a muscarinic antagonist, scopolamine, but not by mecamylamine, a nicotinic antagonist. 5. The PPT effect on cellular and EEG cortical slow oscillation survived, although its duration was reduced, in animals with kainate-induced lesions of thalamic nuclei projecting to areas 5 and 7 (n = 3) as well as in animals with similar excitotoxic lesions leading to extensive neuronal loss in nucleus basalis (n = 2). These data indicate that the PPT effect is transmitted to neocortex through either thalamic or basal forebrain relays.(ABSTRACT TRUNCATED AT 400 WORDS)

Cholinergic influence of K(+)-evoked release of endogenous histamine from rat hypothalamic slices in vitro.

The effects of cholinergic agents on the K(+)-evoked release of endogenous histamine from hypothalamic slices of rats were examined by a superfusion method in vitro. Acetylcholine and carbamylcholine significantly inhibited K(+)-evoked release of histamine from the slices, and the effect of acetylcholine was antagonized by the muscarinic antagonist atropine. On the other hand, nicotine significantly enhanced the K(+)-evoked release and its effect was antagonized by the nicotinic antagonist hexamethonium. The effects of carbamylcholine and nicotine on histamine release from slices of whole hypothalamus and from slices of the anterior hypothalamic region, which do not contain cell bodies of the histaminergic neurons, were the same. Thus, the K(+)-evoked release of endogenous histamine from histaminergic fibers in the hypothalamic slices was inhibited by muscarinic agents and enhanced by nicotinic agents. These results suggest that muscarinic and nicotinic receptors exert antagonistic effects on the release of hypothalamic histamine from in vitro slice preparations. The cholinergic receptors modulating histamine release might be located presynaptically on the histaminergic terminals.