Attention deficit disorder and allergy: A neurochemical model of the relation between the illnesses.

Empirical studies suggest that allergies play an etiological role in a small subgroup of children who suffer from attention deficit-hyperactivity disorder (ADHD). Research indicated that allergic reactions result in cholinergic hyperresponsiveness and beta-adrenergic hyporesponsiveness in the autonomic nervous system. Evidence is reviewed that similar imbalances in central nervous system cholinergic/adrenergic activity play a causal role in manic and depressive behaviors. It is hypothesized that allergic reactions engender cholinergic/adrenergic activity imbalances in the central nervous system, leading to poorly regulated arousal levels and ADHD behaviors in some children. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A histochemical study of the innervation of cerebral blood vessels in the snake

Dual innervation of snake cerebral blood vessels by adrenergic and cholinergic fibres was demonstrated with the use of histochemical methods. Although the nerve plexuses are somewhat less dense, the essential features of innervation of the blood vessels are similar to those of mammals with the exception that the adrenergic plexuses are more prominent than the cholinergic plexuses. The major arteries of the cerebral carotid system have a rich nerve supply. However, the innervation is less rich in the basilar and poor in the spinal (vertebral) arteries. Although the arteries supplying the right side of head are poorly developed, three pairs of arteries, cerebral carotids, ophthalmics and spinals, supply the snake brain. The carotids and ophthalmics are densely innervated and are accompanied by thick nerve bundles, suggesting that the nerves preferentially enter the skull along those arteries. Some parenchymal arterioles are also dually innervated. Connection between the brain parenchyma and intracerebral capillaries via both cholinergic and adrenergic fibres was observed. In addition cholinergic nerve fibers, connecting capillaries and the intramedullary nerve fibre bundles, were noticed. Capillary blood flow may be influenced by both adrenergic and cholinergic central neurons. The walls of capillaries also exhibit heavy acetylcholinesterase activity. This may indicate an important role for the capillary in the regulation of intracerebral blood flow.     

Nervous regulation of the tone of the retractor penis muscle in the goat

The nervous control of the retractor penis muscle (rp) was investigated in the anaesthetized goat. Also, isolated field stimulated strips of the muscle were studied. The noradrenaline (NA) and acetylcholine (ACh) content of the rp was determined, and histochemistry for adrenergic and acetylcholinesterase (AChE) positive nerves was performed. The muscle exhibited spontaneous activity that persisted after section of all nerves. There was, however, also a tendency of the activity to follow the general vasomotor tone, which disappeared after section of the sympathetic chains. The excitatory adrenergic nerves which innervate the muscle come from the sympathetic chains and run along the pudendal, the hypogastric and the pelvic nerves. The rp has a dense network of adrenergic fibres and is very sensitive to excitatory adrenergic stimulation. It has a fairly large NA content, which is higher in old goats (5.95 +/- 0.42 micrograms g-1) than in young goats (2.87 +/- 0.78 micrograms g-1). Inhibitory non-adrenergic non-cholinergic (NANC) innervation reaches it via the pelvic and the hypogastric nerves. The maximum inhibitory response is reached at low frequencies (2-4 Hz). Cholinergic prejunctional inhibition of the excitatory response to sympathetic chain stimulation was effected by simultaneous stimulation of the hypogastric nerves. In vitro experiments confirmed the presence of endogenous cholinergic muscarinic suppression of the excitatory adrenergic neurotransmission. Significant amounts of ACh (0.81 +/- 0.18 micrograms g-1) are present in the muscle, and it contains strongly AChE positive nerve fibres and nerve cell bodies. It is concluded that the goat rp is innervated by sympathetic adrenergic excitatory nerves and parasympathetic NANC inhibitory nerves. It further has a direct sympathetic inhibitory NANC innervation, and an indirect inhibitory cholinergic innervation which at least in part is sympathetic.     

Histophysiologic characteristics of the effector innervation of the arteries of the base of the brain during rat ontogenesis

The development of adren- and cholinergic nervous plexuses in the brain base arteries was studied by histochemical methods of Falck and Kelle in animals and fetuses of 10-22 days, newborn rats, animals of 10, 20, 30, 40, 60 and 120 days of life and 1 and 2 years old rats. The cholinergic nerve fibres were first found in the basilar, vertebral and internal carotid arteries on the 15th and 16th days of ontogenesis. Specific fluorescence of adrenergic conductors on the same arteries is revealed somewhat later--from the 17th and 18th days of the intrauterine development. Further formation of the cholin- and adrenergic innervation of the arteries of the Willis' circle goes on synchronously. The number of nerve fibres increases with the growth of the artery diameter. The concentration of catecholamines and the activity of AChE in them gradually increases. The greatest density of nerve fibres per 1 mm2 is determined in 20-day-old rats. The number of cholinergic nerve fibres on the arteries of the brain base is equal to that of adrenergic fibres during the whole period of postnatal ontogenesis. By the 30th day the effector nervous apparatus has a definite structure. In old rats the activity of AChE and the content of catecholamines drop, the amount and concentration of nerve fibres decrease.     

Cholinergic innervation of vessels of the base of the brain

Distribution and activity of acetylcholinesterase in the intramural nerve apparatus of vessels of the base of the bran have been studied with the histochemical method of Koelle-Gomori. On the whole, 268 arteries have been examined. The activity of the ferment is detected in the effector nerve fibers in the wall of all cerebral vessels constituting the system of the circle of Willis. The periarterial nerve apparatus of cerebral arteries of the anterior and posterior regions of the circle of Willis consists of two cholinergic plexuses - superficial and deep plexus forming a multilayered neural cover. The terminal parts of cholinergic nerve fibres at the border with the muscular coat show a granular structure. Moreover, nerve cells rich in active ferment are found in the cholinergic plexuses. Difference in the character of cholinergic innervation of vessels of the internal carotid and the vertebrobasilar region has been shown. The obtained data indicate that the vessels of the circle of Willis possess a reliable cholinergic system of nerve regulation which along with other systems, such as that of adrenergic nerve fibers, maintains the homeostasis of the cerebral blood flow.     

Visceral Afferent Bias on Cortical Processing: Role of Adrenergic Afferents to the Basal Forebrain Cholinergic System.

Intraperitoneal epinephrine enhances the cerebral auditory evoked potential (AEP), an effect that is dependent on the basal forebrain cortical cholinergic system. The present study examined the hypothesis that ascending noradrenergic projections from brainstem autonomic substrates to the basal forebrain cholinergic system represent an essential component of the ascending pathway mediating this effect of epinephrine. Epinephrine again enhanced the AEP in rats, and this effect was attenuated by infusion of the selective α1 adrenergic antagonist terazosin into the basal forebrain. Moreover, infusions of the selective α1 adrenergic agonist phenylephrine into the basal forebrain mimicked the priming effects of epinephrine. Results support the hypothesis that noradrenergic afferents to the basal forebrain cholinergic system represent a component of an ascending visceral afferent system. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Autonomic-somatic relationships: Blockade of heart rate and corneo-retinal potential responses.

Studied unconditioned heart rate (HR) response and conditioned HR and corneo-retinal potential (CRP) responses of a total of 75 naive New Zealand rabbits. 4 experiments were performed under conditions of cholinergic (muscarinic) and beta adrenergic and double blockades in which both adrenergic and cholinergic agents were combined. Results indicate that (a) the HR UCR was an acceleration, whereas the CR was a deceleration in rate; (b) both HR CRs and UCRs were decreased by the individual administration of adrenergic and cholinergic blockades and completely abolished by double blockades; (c) both blockades also decreased CRP conditioning, and the double blockade abolished CRP CRs; (d) although HR blockade by the peripheral cholinergic agent, methylatropine, and the centrally acting atropine sulfate were comparable, CRP CRs occurred after methylatropine administration but were almost completely abolished by atropine sulfate. (27 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Development of choline acetyltransferase and cholinesterase activities in enteric ganglia derives from presumptive adrenergic and cholinergic levels of the neural crest

The cholinergic differentiation of enteric ganglia in embryos of chick and quail was studied with particular reference to cholinesterase and choline acetyltransferase activities. Differentiation during normal development was compared with that obtained after culture of the neural primordium or neural crest in direct association with aneural hindgut. Biochemically differentiated cholinergic ganglia developed in explants containing cells from either the 'vagal' (presumptive cholinergic) or 'truncal' (presumptive adrenergic) levels of the neural crest. Neither extra-intestinal migration of neural crest cell nor the presence of central preganglionic fibres is a prerequisite for enteric ganglion differentiation.     

Airway autonomic nervous system dysfunction and asthma

Airways are richly innervated by 4 nervous systems: adrenergic, cholinergic, inhibitory nonadrenergic noncholinergic (i-NANC), and excitatory NANC (e-NANC) nervous systems. Dysfunction or hyperfunction of these systems may be involved in the inflammation or airway hyperresponsiveness observed in asthmatic patients. The cholinergic nervous system is the predominant neural bronchoconstrictor pathway in humans. Airway inflammation results in exaggerated acetylcholine release from cholinergic nerves via dysfunction of the autoreceptor, muscarinic M2, which is possibly caused by a major basic protein or IgE. Vasoactive intestinal peptide (VIP) and nitric oxide (NO) released from i-NANC nerves act as an airway smooth muscle dilator. The effects of VIP and NO are diminished after allergic reaction by inflammatory cell-mediated tryptase and reactive oxygen species. Thus, in asthmatic airways, the inflammatory change-mediated neural imbalance may result in airway hyperresponsiveness. Tachykinins derived from e-NANC nerves have a variety of actions including airway smooth muscle contraction, mucus secretion, vascular leakage, and neutrophil attachment; and they may be involved in the pathogenesis of asthma. Since tachykinin receptor antagonists are effective for bradykinin- and exercise-induced bronchoconstriction in asthmatic patients, these drugs may be useful for asthma therapy.     

Adrenergic innervation of the cerebral arteries following changes in the activity of cholinergic and monoaminergic brain systems

Bipolar electrical nerve stimulation decreased the adrenergic innervation density and the catecholamine content in the rat isolated caudal artery. Changes in cholinesterase activity and catecholamine content in histochemically active nerves following administration of cholinesterase (AChE) inhibiting agent phosphacol, seem to reflect compensatory responses to increasing dilatory cholinergic vasomotor effects under conditions of the AChE activity. Adrenergic innervation of cerebral arteries was also studied after a 1-hr daily hypoxic sessions. These decreased the catecholamines content as compared to the control.     

Efficacy of octreotide in diarrhoea due to Vibrio cholerae: a randomized, controlled trial

The ultrastructure of autonomic nerve fibers and terminal varicosities is described in relation to the lamina propria of the human seminiferous tubules during childhood (age 3 to 10 years). Autonomic nerve varicosities are classified as: Type I with numerous small (30-60 nm) agranular vesicles and variable numbers of large (100 nm) granular vesicles, and Type II with numerous small (30-60 nm) granular vesicles and sporadic large granular vesicles. These two varicosity types are consistent in morphology with cholinergic and adrenergic nerve terminals, respectively. Nerve varicosities are found, associated with Schwann cells, in proximity to the cells of the lamina propria. Although not found in direct "synaptic' contact, these autonomic endings are often within a few hundred nanometers of the cellularity of the lamina propria. The Schwannian sheath is interrupted over the varicosities at these sites and occasionally the terminal varicosities are totally lacking a Schwann sheath. These findings are consistent with the structural relationship of autonomic nerve "terminals' and effector in other endocrine and non-endocrine systems. This is the first evidence of adrenergic nerve varicosities in proximity to the lamina propria in humans (at any age). Evidence is also presented which suggests a locational difference in the distribution of cholinergic (Type I) and adrenergic (Type II) nerve varicosities in this region, with only cholinergic endings observed directly adjacent to the basal lamina of the seminiferous tubules.     

Long-term observations of uterine contractions in nonpregnant dogs

Uterine contractile activity in nonpregnant conscious dogs was investigated based on 2- to 6-mo-long continuous recording by means of a chronically implanted force transducer. We found that nonpregnant uterine contractile activity could be classified into six major patterns: sporadic contractions, weak and strong tonic contractions, weak and strong phasic contractions, and phasic contraction bursts. The contractile patterns during proestrus and estrus were the most active, with strong phasic and tonic contractions and phasic contraction bursts. The phasic and tonic contractions were inhibited dose-dependently by a beta 2 adrenergic agonist, ritodrine, and reproduced by an alpha 2 adrenergic agonist, clonidine. In contrast, the cholinergic inhibitors atropine and hexamethonium did not affect the spontaneous occurrence of these contractions, although bethanechol evoked uterine contractions. Oxytocin and prostaglandin F2 alpha-induced contractions were phasic during estrus, whereas they showed tonic increases with phasic contractions during proestrus, diestrus, and anestrus, and these contractions did not resemble the spontaneous contractions. In conclusion, the nonpregnant uterus contracts continuously in harmony with the estrous cycle phases, and its contractile activity is enhanced by alpha adrenergic receptors and inhibited by beta 2 adrenergic receptors.     

Differential and coordinated regulation of expression of norepinephrine transporter in catecholaminergic cells in culture

The norepinephrine transporter (NET) terminates noradrenergic neurotransmission at synapse by high-affinity sodium-dependent reuptake into presynaptic terminals, and thus serves as a marker of differentiation of noradrenergic neurons. In the present study, we studied the regulatory mechanism of the expression of NET-mRNA in cultured neurons from newborn rat superior cervical ganglia (SCG) and in clonal rat pheochromocytoma cells (PC12) SCG neurons in culture expressed a high level of NET-mRNA, which was further increased 2.5-5 fold from day 1 to day 13. Treatment of SCG neurons with the cholinergic differentiation factor (CDF)/leukemia inhibitory factor (LIF) and ciliary neurotrophic factor (CNTF), neurokines known to induce the switch from adrenergic to cholinergic phenotype in SCG neurons, led to the suppression of the level of NET-mRNA in a concentration dependent manner, concomitantly with the suppression of mRNA for tyrosine hydroxylase (TH), an adrenergic marker enzyme in cultured SCG neurons. On the other hand, retinoic acid, a compound which is also known to increase the expression of choline acetyltransferase, a cholinergic marker enzyme, and suppress the expression of TH in the cultured SCG neurons and PCI2 cells, rather increased the level of NET-mRNA in these two cell populations. Alterations of the Na(+)-dependent norepinephrine transport activity which paralleled the changes in the NET-mRNA levels were confirmed by the [3H]norepinephrine uptake assay. These results indicate that cell extrinsic factors regulate the expressions of NET and TH genes by a common as well as by distinct mechanisms.     

Pontine cholinergic respiratory depression in neonatal and young rats

We postulated that activation of pontine cholinergic mechanisms would cause respiratory depression in neonatal and young rats. Phrenic activity was recorded in decerebrate, paralyzed, ventilated and vagotomized rats of 4 to 22 days after birth. Small volumes (10-60 nl) of carbachol (44-88 mM) were injected into the medial portion of the rostral pons. The injection of carbachol, but not saline, decreased phrenic peak activity (83 +/- 6% of control) and respiratory frequency (64 +/- 9.5% of control) within 2 min following the injection in neonates and the depression lasted for less than 10 min. The site of injection in the pontine reticular formation was confirmed by histology. Results suggest that cholinergic mechanisms in the medial pons depress respiratory activity in the neonate.     

Electroencephalographic responses to photic stimulation in habitual smokers and nonsmokers.

Performed 2 studies in which EEGs of 45 habitual cigarette smokers and of 59 nonsmokers were taken before and after they were required to smoke a cigarette. The EEGs were scored for incidence of EEG "driving" responses to photic stimulation, an index that appears to reflect the balance between central adrenergic and cholinergic nervous systems. Findings suggest that smokers tend to have a central autonomic balance less in favor of adrenergic functioning than do nonsmokers. Cigarette smoking may alleviate a possible central adrenergic insufficiency of smokers. These findings suggest a solution to "Nesbitt's paradox," which has reference to the fact that while nicotine is a central adrenergic stimulant, smokers describe the effect of smoking in sedational terms (i.e., as relaxing or calming). (22 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Adrenergic/cholinergic immunomodulation in the rat model--in vivo veritas?

For several years, our group has been studying the in vivo role of adrenergic and cholinergic mechanisms in the immune-neuroendocrine dialogue in the rat model. The main results of these studies can be summarized as follows: (1) exogenous or endogenous catecholamines suppress PBL functions through alpha-2-receptor-mediated mechanisms, lymphocytes of the spleen are resistant to adrenergic in vivo stimulation, (2) direct or indirect cholinergic treatment leads to enhanced ex vivo functions of splenic and thymic lymphocytes leaving PBL unaffected, (3) cholinergic pathways play a critical role in the "talking back" of the immune system to the brain, (4) acetylcholine inhibits apoptosis of thymocytes possibly via direct effects on thymic epithelial cells, and may thereby influence T-cell maturation, (5) lymphocytes of the various immunological compartments were found to be equipped with the key enzymes for the synthesis of both acetylcholine and norepinephrine, and to secrete these neurotransmitters in culture supernatants.     

Dopaminergic and cholinergic influences on motor behavior in chickens.

Examined the effects and interactions of apomorphine (AP; 0–4.0 mg/kg, ip), haloperidol (HAL; 0–2.0 mg/kg, ip), scopolamine (SCO; 0–2.0 mg/kg, ip), and pilocarpine (PIL; 0–50 mg/kg, ip) on stabilimeter activity and tonic immobility in White Leghorn?×?Black Australorp male chickens. The dopamine receptor agonist AP enhanced motor activity and decreased the duration of tonic immobility behavior in a dose-dependent manner. HAL, a dopamine receptor antagonist, increased the duration of tonic immobility and attenuated AP-induced increase in activity. Motor activity could also be increased by the cholinergic antagonist SCO. In addition SCO decreased the duration of tonic immobility. On the other hand, the cholinergic agonist PIL increased tonic immobility behavior and decreased SCO's effect on motor activity. Studies of the interaction of dopaminergic and cholinergic systems showed that HAL could attenuate the activity-stimulating effects of SCO, whereas PIL had a similar, but lesser, effect on AP-induced activity. Results support the suggestion that in birds, as in mammals, the dopaminergic and cholinergic systems are intimately involved in the expression of motor behavior. (40 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Boosting cholinergic activity in gustatory cortex enhances the salience of a familiar conditioned stimulus in taste aversion learning.

The cholinergic system is important for learning, memory, and responses to novel stimuli. Exposure to novel, but not familiar, tastes increases extracellular acetylcholine (ACh) levels in insular cortex (IC). To further examine whether cholinergic activation is a critical signal of taste novelty, in these studies carbachol, a direct cholinergic agonist, was infused into IC before conditioned taste aversion (CTA) training with a familiar taste. By mimicking the cholinergic activation generated by novel taste exposure, it was hypothesized that a familiar taste would be treated as novel and therefore a salient target for aversion learning. As predicted, rats infused with the agonist were able to acquire CTAs to familiar saccharin. Effects of carbachol infusion on patterns of neuronal activation during conditioned stimulus–unconditioned stimulus pairing were assessed using Fos-like immunoreactivity (FLI). Familiar taste–illness pairing following carbachol, but not vehicle, induced significant elevations of FLI in amygdala, a region with reciprocal connections to IC that is also important for CTA learning. These results support the view that IC ACh activity provides a critical signal of taste novelty that facilitates CTA acquisition. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Short-term versus long-term effects of adrenal hormones on behaviors.

Hypothesizes that short-term exposures to stress facilitate performances of serially repetitive, overlearned tasks and impair performances of perceptual restructuring tasks, while long-term exposures to stress produce the opposite behavioral effects. These effects are attributed, in part, to the length of exposure of the central nervous system to stress-elicited adrenal hormones (epinephrine and cortisol). Short-term exposures are believed to induce states of central adrenergic dominance that favor performances of serially repetitive, overlearned tasks at the expense of perceptual restructuring tasks. Longer exposures are thought to result in a shift to central cholinergic dominance that favors the opposite pattern of performances. A physiological model is presented that accounts for the shift from central adrenergic to central cholinergic dominance. Experimental procedures derived from the model promote the reversal of some of the behavioral and physiological effects of a long-term stressor. (5 p ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Central and peripheral cholinergic involvement in the habituation of investigatory head poking in rats.

Studied the effects of some centrally and peripherally acting cholinergic agonists and antagonists on locomotor exploration and investigatory head poking in 2 experiments with 114 male Lister hooded rats. An apparent disruption of within-trials habituation of locomotion and head-poke frequency was demonstrated for arecoline, nicotine, carbachol, scopolamine, and methylscopolamine (all administered ip). It is suggested that the effect may be a consequence of a drug-induced depression of initial activity. When this factor was eliminated, both scopolamine and methylscopolamine showed some slight attenuation of habituation. The increase in head-poke duration over time in controls was blocked by scopolamine; although peripheral factors were involved, the scopolamine effect had a significant central component. Results are discussed in relation to hypothetical links between the cholinergic system and habituation. (19 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)