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PubMed1988

Monitoring of brain function by means of evoked potentials in cerebral aneurysm surgery.

Deliberate arterial hypotension is currently used to operate upon cerebral aneurysms. However, it is not ascertained whether this practice is really safe for all patients, especially those presenting with preoperative vasospasm. 50 patients, requiring surgical treatment for cerebral aneurysm, have been submitted, during surgery, to the recording of Somatosensory Evoked Potentials (SEPs) on median nerve stimulation. This technique allows the functional evaluation of neural pathways mediating the somatosensory stimuli and of primary somatosensory cortex; it is known that a decrease of cerebral perfusion may affect the SEP waveforms in terms of reduced subcortical conduction velocity (i.e., increased central conduction time, CCT) and of reduced cortical response amplitude. These changes may be apparent before a permanent neurological damage is produced. Preoperative SEP recording demonstrated a prolonged CCT, possibly related to vasospasm, in 9 patients, a normal clinical evaluation notwithstanding (grade I and II). During intraoperative deliberate hypotension, a SEP change has always been produced. No postoperative damage has been observed, however, as long as the CCT did not exceed 9 msec for 10 minutes (maximum normal CCT value is 6.7 msec) and as the cortical response had been visible throughout the whole surgical procedure. The critical value of CCT has been reached at a mean arterial pressure (MAP) lower than 60 Torr in patients with a normal preoperative SEP recording; at the opposite, in patients presenting with a prolonged preoperative CCT, the value of 9 msec was arrived at with a MAP value that is generally accepted as safe for all patients (75 Torr).(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia↗

PubMed1994

Maturation of nonadrenergic noncholinergic inhibitory system in normal and allergen-sensitized rabbits.

We investigated the functional existence of the nonadrenergic noncholinergic inhibitory (NANCi) system in developing rabbit airways in vitro. Furthermore, we evaluated the effect of parenteral exposure to a specific allergen (ragweed) on the maturation of this neural pathway. NANCi responses were studied on tracheal smooth muscle (TSM) segments obtained from normal and ragweed-sensitized New Zealand White rabbits at 1, 2, 4, and 12 wk of age. The TSM segments were removed and placed in tissue baths containing modified Krebs-Henseleit solution, atropine (1 x 10(-5) M), and propranolol (5 x 10(-6) M). After contraction with neurokinin A (1 x 10(-5) M), electrical field stimulation was applied at stimulation frequencies ranging from 5 to 30 Hz to determine the frequency that produced maximal relaxation. The NANCi response to EFS was measured and expressed as the mean (+/- SE) percent relaxation at 20 Hz, because this stimulation frequency gave the maximal NANCi response at each age studied. TSM segments obtained from control rabbits at 1 wk of age did not demonstrate a NANCi response at the frequencies of stimulation used. By contrast, a reproducible NANC relaxation was demonstrated in TSM from 2-, 4-, and 12-wk-old rabbits. The magnitude of this response was 27 +/- 4.7 (n = 10), 29 +/- 4.8 (n = 9), and 37 +/- 4% (n = 18), respectively. The same experiments performed on TSM segments obtained from ragweed-sensitized animals gave significantly decreased values of NANCi response. In 2-, 4-, and 12-wk-old rabbits, the NANCi responses were 11.5 +/- 3.4 (n = 9), 11 +/- 2 (n = 13), and 16 +/- 4.2% (n = 14).(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗

PubMed1997

Differential control of reciprocal inhibition during walking versus postural and voluntary motor tasks in humans.

Experiments were done to determine whether the strength of reciprocal inhibition from ankle flexors to extensors can be controlled independently of the level of ongoing motor activity in a task-dependent manner. In this paper we use the term reciprocal inhibition in the functional sense--inhibition of the antagonist(s) during activity of the agonist(s)--without reference to specific neural pathways that may be involved. The strength of reciprocal inhibition of the soleus alpha-motoneurons was determined by measuring the amplitude of the H reflex during voluntary, postural, and locomotor tasks requiring activity of the ankle flexor tibialis anterior (TA). Differences in the strength of reciprocal inhibition between tasks were determined from plots of the soleus H reflex amplitude versus the mean value of the TA electromyogram (EMG). Additionally, in tasks involving movement, the correlation between the H reflex amplitude and the joint kinematics was calculated. In most subjects (15 of 22) the soleus H reflex decreased approximately linearly with increasing tonic voluntary contractions of the TA. The H reflex also decreased approximately linearly with the TA EMG activity when subjects where asked to lean backward. There were no statistical differences between the regression lines obtained in these tasks. In some subjects (7 of 22), however, the H reflex amplitude was independent of the level of TA EMG activity, except for a sudden drop at high levels of TA activity (approximately 60-80% of maximum voluntary contraction). The type of relation between the soleus H reflex and the TA EMG activity in these tasks was not correlated with the maximum H reflex to maximum M wave (Hmax/Mmax) ratio measured during quiet standing. In marked contrast, during the swing phase of walking--over the same range of TA EMG activity as during the tonic voluntary contraction task--the H reflex was reduced to zero in most subjects (24 of 31). In seven subjects the H reflex during the swing phase was reduced to some 5% of the value during quiet standing. The same result was found when subjects were asked to produce a stepping movement with one leg (OLS) in response to an auditory "go" signal. Additionally, in the OLS task it was possible to examine the behavior of the H reflex during the reaction time and thus to evaluate the relative contribution of central commands versus movement-related afferent activity to the inhibition of the soleus H reflex. In 11 of 12 subjects the H reflex attained its minimum value before either the onset of EMG activity or movement of any of the leg joints. It is significant that the H reflex was most powerfully inhibited during the swing phase of walking and the closely related OLS task. The H reflex was also measured during isolated ankle dorsiflexion movements. The subjects were asked to track a target displayed on a computer screen with dorsiflexion movements of the ankle. The trajectory of the target was the same as that of the ankle during the swing phase of walking. The soleus H reflexes were intermediate in size between the values obtained in the tonic contraction task and the walking or OLS tasks. A negative, but weak, correlation (r2 < 0.68) between the soleus H reflex and the TA EMG was found in 3 of 10 subjects. Furthermore, there was no correlation between the H reflex amplitude and the ankle angular displacement or angular velocity. In this task, as in the OLS task, the H reflex began to decrease during the reaction time before the onset of TA EMG activity. We conclude that the strength of reciprocal inhibition of the soleus alpha-motoneuron pool can thus be controlled independently of the level of motor activity in the ankle flexors. The strength of the inhibition of the antagonist(s) depends on the task, and for each task the strength of the inhibition is not necessarily proportional to the level of motor activity in the agonist(s). (ABSTRACT TRUNCATED)

Adult↗

PubMed1999

The pathology of shingles: Head and Campbell's 1900 monograph.

Shingles (herpes zoster) and postherpetic neuralgia, a chronic neuropathic pain syndrome that can persist after the shingles lesions heal, were studied by eminent neurologists of the 19th century. Autopsy studies were used to establish sensory neural pathways in the peripheral and central nervous systems. More recently, zoster and postherpetic neuralgia have served as models for the study of the pathogenesis and treatment of neuropathic pain. Postherpetic neuralgia has the cardinal clinical features of all neuropathic pain syndromes, including sensory abnormalities, ongoing pain, and allodynia (touch-induced pain). Unlike most other neuropathic pain syndromes, such as trigeminal neuralgia or nerve root compressions, shingles has a well-defined pathogenesis and onset, as well as visible lesions, and is therefore uniquely suitable for study.

Herpes Zoster↗

PubMed2006

Frequency-dependent reciprocal modulation of verbal fluency and motor functions in subthalamic deep brain stimulation.

BACKGROUND: High-frequency deep brain stimulation (DBS) of the subthalamic nucleus (STN) improves motor functions in those with Parkinson disease but may worsen frontal functions such as verbal fluency (VF). In contrast, low-frequency DBS leads to deterioration of motor functions. It is not known whether low-frequency STN DBS also has an effect on frontal functions. OBJECTIVE: To examine whether low-frequency STN DBS in contrast to high-frequency STN DBS has a positive effect on frontal functions on the basis of VF test results. DESIGN: A double-blind randomized crossover experiment to compare performance in 4 VF subtests and motor performance at 10 Hz, 130 Hz, and no stimulation. SETTING: University hospitals in Düsseldorf and Cologne, Germany. PATIENTS: Twelve patients with Parkinson disease 3 months or more after bilateral electrode implantation into the STN. MAIN OUTCOME MEASURE: Mean number of words in VF at different stimulation frequencies. RESULTS: The VF was significantly better at 10 Hz (48.3 words) compared with 130 Hz and showed a nonsignificant trend toward worsening at 130 Hz (42.3 words) compared with no stimulation (43.8 words). These results were consistent across all subtests. CONCLUSIONS: The study provides evidence of a beneficial effect of low-frequency (10 Hz) STN DBS on VF, which may be caused by activating neural pathways projecting to the frontal cortex. In addition, the study reproduces the negative effect of therapeutic high-frequency STN DBS on VF. The study results provide evidence for a frequency-dependent modulation of cognitive circuits involving the STN.

Aged↗

PubMed1977

Signs of essential blepharospasm: a motion-picture analysis.

Motion pictures of 15 patients with essential blepharospasm were studied. Previously unrecognized signs indicated multiple cranial nerve involvement. These signs include impersistence of gaze, lid retraction, tongue thrust, head tilts, head jerks, vertical gaze spasms, and asymmetry. The sugns were also observed in a patient with bilateral blepharospasm who had a history of Bell's palsy suggesting facial nerve injury as a possible factor in blepharospasm. The presence of these signs can be explained by known neural pathways, but the site, or sites, of the lesion remains obscure. These signs may be important in assessing severity and in treatment evaluation.

Adult↗

PubMed1987

Psychophysical and electroretinographic findings in X-linked juvenile retinoschisis.

We compared psychophysical and electroretinographic test results of four patients with X-linked juvenile retinoschisis who had clinically apparent lesions isolated to the foveal area. The b-wave of the flash electroretinogram was selectively reduced, while the a-wave was within the normal range. Oscillatory potentials generated by either the rod or cone systems were markedly reduced. Absolute thresholds outside the fovea were either normal or only moderately elevated, indicating that the sensory neural pathways were, by and large, operating with limited dysfunction. Therefore, the oscillatory potentials do not directly reflect, to any appreciable extent, the function of bipolar or ganglion cells. Finally, a sequence of pathologic events is proposed for X-linked juvenile retinoschisis that initiates with Müller cell dysfunction.

Adolescent↗

PubMed1990

Sarcoidosis as a cause of left recurrent laryngeal nerve palsy.

Vocal cord paralysis is an unusual complication of sarcoidosis. Sarcoidosis may affect vocal cord function by either direct involvement of the cord or by involvement of the neural pathways, including the nucleus ambiguous, the 10th cranial nerves, and the superior and recurrent laryngeal nerves. There have been only two previous case reports of sarcoidosis with mediastinal adenopathy causing compression of the left recurrent laryngeal nerve and vocal cord paralysis. We present a third such case.

Humans↗

PubMed1997

Intraoperative mapping of sensate flaps. Electrophysiologic techniques and neurosomal boundaries.

BACKGROUND: The desirability of restoring sensation to the upper aerodigestive tract has led to an expanded use of sensate flaps for reconstruction of mucosal defects. Sensation can be restored via preformed neural pathways through the anastomosis of recipient and donor nerves, provided that the sensate flap falls within the boundaries of the neurosome for the identified sensory nerve. OBJECTIVES: To perform detailed electrophysiologic mappings of neurosomes of potential sensate flap donor sites, to describe their variability, and to investigate the usefulness of intraoperative mapping in terms of flap design and harvesting. DESIGN: A case series of 27 patients who were undergoing free flap reconstruction of various postablative head and neck defects were examined. Two silver-silver chloride recording electrodes were placed in direct contact with the dissected sensory nerve, and the overlying skin was either mechanically or electrically stimulated. Auditory feedback, as well as visualization of the responses on an oscilloscope, determined whether the stimulated area fell within the neurosome. This technique was applied to the lateral antebrachial cutaneous nerve of the radial forearm flap (n = 15), the lateral sural cutaneous nerve of the fibula flap (n = 5), the subcostal nerve of the iliac crest flap (n = 6), and the dorsal cutaneous rami of spinal nerve T-1 or T-2 of the scapula flap (n = 1). RESULTS: The neurosome of the lateral antebrachial cutaneous nerve was relatively consistent with the variability only at the distal boundary (ie, the dorsum of the hand). The neurosome of the lateral sural cutaneous nerve was more variable, falling into 2 distinct innervation patterns: one showing innervation that was limited to the upper lateral and posterior portions of the calf and the other demonstrating significant extension into the lower half of the calf. The neurosome of the subcostal nerve showed little variability and consistently overlapped the proposed skin paddle. The neurosome of the T-1 or T-2 spinal nerve was mapped in 1 patient and is described. CONCLUSIONS: The consistency of neurosomal boundaries is dependent on the donor site. Intraoperative mapping of flap donor sites may not only assure the harvesting of a true sensate flap, but may also allow for intraoperative decision making with regard to possible modifications of flap design and harvesting techniques. Two new sensate flaps from the iliac crest and scapula are accurately described.

Adult↗

PubMed2000

Expression of chondroitin sulfate proteoglycans in the chiasm of mouse embryos.

Chondroitin sulfate (CS) proteoglycans have been implicated as molecules that are involved in axon guidance in the developing neural pathways. The spatiotemporal expression of CS was investigated in the developing retinofugal pathway in mouse embryos by using the CS-56 antibody. Immunoreactive CS was detected in inner regions of the retina as early as embryonic day 11 (E11). Its expression in subsequent stages of development followed a centrifugal, receding gradient that appeared to correlate with the sequence of axogenesis in the retina. In the chiasm, immunoreactive CS was expressed at E12, before the arrival of retinal axons. When the retinal axons navigated in the chiasm at E13-E14, immunoreactive CS remained at a low level in the optic fiber layer of the chiasm but was observed prominently in the caudal parts of the ventral diencephalon. This pattern followed closely the array of stage-specific-embryonic-antigen-1-positive neurons in the ventral diencephalon, with a V-shaped configuration that bordered the posterior boundary of the retinal axons, and a rostral raphe extension that ran across the decussating axons in the chiasm. Thus, the CS epitope is implicated in patterning the course of early retinal axons and in regulating axon divergence in the chiasm. At the lateral region of the chiasm, where the retinal axons cross the midline and approach the optic tract, a CS-immunopositive region coincided with the region in which active sorting of dorsal retinal axons from ventral retinal axons occurs. Moreover, at the threshold of the optic tract, the immunoreactive CS was restricted only to the deep part of the optic fiber layer, suggesting an inhibitory role of the CS epitope in repelling newly arrived axons to superficial regions of the optic tract during the development of chronotopic order at this part of the retinofugal pathway.

Animals↗

PubMed1997

Comparative histology of pulmonary neuroendocrine cell system in mammalian lungs.

It is increasingly recognized that neuroepithelial endocrine cells and organoid clusters of these cells termed neuroepithelial bodies are widely distributed in the respiratory tract of vertebrates. This review focuses on the neuroepithelial endocrine system in the airway epithelium of mammals according to observations made in a wide range of species, as it appears in light and electron microscopy by means of various visualization techniques under normal and experimental conditions. Because there are similarities but also marked differences between species, wherever possible studies in human airways are emphasized. Conventional histochemical and ultrastructural studies including microspectrofluorimetry have demonstrated the amine-handling properties and the presence of neurosecretory granules in neuroendocrine cells of the epithelium of all mammals studies so far. The neuroepithelial bodies are innervated by morphological afferent- and efferentlike synaptic specializations. These, together with the presence of reciprocal synapses, emphasize that these cells may be involved in dual functions of chemoreception and secretion. Light and electron microscopic immunohistochemistry has demonstrated that neuroepithelial endocrine cells may contain various biogenic agents, suggesting that the neuroendocrine system is highly heterogeneous. Neural elements may interact in a complex manner, and the activation of certain neural pathways may control the release of biogenic substances to influence physiological airway functions. They may be particularly relevant in pulmonary diseases. Consequently, the function of this system is complex and it is highly probable that many of its aspects are still not elucidated.

Animals↗

PubMed1999

Course and composition of the nerves that supply the mandibular teeth of the rat.

The rodent dentition has become an important model for investigations of interactions between dental tissues and peripheral neurons. Although experimental nerve injury has been widely used for such studies, there is uncertainty about the courses of nerve fibers supplying the mandibular teeth. In order to clarify this, we used a mixture of monoclonal antibodies against neurofilament proteins to enhance demonstration of nerve fibers so that small nerves could be readily traced in serial frozen sections of mandibles of Sprague Dawley rats ranging in age from embryonic day (E) 18 to postnatal day (P) 90. The 1st molar and anterior portion of the 2nd molar were innervated by small nerves that emerged as distinct branches of the IAN trunk at or near the mandibular foramen. In contrast, the nerve supply to the 3rd molar and posterior part of the 2nd molar was a branch of the lingual nerve that bypassed the mandibular canal altogether. The IAN trunk split into the mental nerve and a large branch to the incisor about 2 mm anterior to the mandibular foramen. Thick branches of the incisor nerve descended into the incisor socket to form a dense plexus of nerve fiber bundles extending along the length of the incisor periodontium. The sparse pulpal innervation of the incisor was provided by a few thin fascicles that emerged from the caudal portion of the periodontal plexus to enter the incisor apex. The dental branches of the IAN and lingual nerve seen in the adult were well established and readily identifiable at age E18 even though their targets were limited to the follicles of the developing teeth. These studies show that the trigeminal branches that supply the mandibular teeth can be identified at a wide range of ages as distinct nerves at a considerable distance proximal to their targets. This detailed information on the courses taken by the dental nerves can provide an anatomical basis for increased precision in characterization and perturbation of neural pathways from the molars and incisor.

Animals↗

PubMed1997

Prenatal exposure to moderate levels of ethanol can have long-lasting effects on hippocampal synaptic plasticity in adult offspring.

Prenatal ethanol exposure has been associated with long-lasting intellectual impairments in children. Previous studies using animal models of fetal ethanol exposure suggest that these deficits are, at least in part, linked to neurochemical abnormalities in the hippocampal formation. We explored whether prenatal exposure to moderate quantities of ethanol produced functional deficits at the entorhinal cortical perforant path-dentate granule cell connection by examining some electrophysiological properties, including the induction of long-term potentiation (LTP). Rat dams consumed one of three diets throughout gestation: 1) a BioServ liquid diet containing 5% (v/v) ethanol (26% ethanol-derived calories), which produces a maternal peak blood ethanol concentration of 83 mg/dl; 2) pair-fed an isocalorically equivalent amount of 0% ethanol liquid diet; or 3) Purina rat chow ad libitum. Adult offspring (120-150 days of age) from each experimental diet group were anesthetized with urethane and field excitatory postsynaptic potentials (EPSPs) and population spikes were measured in the dentate gyrus in response to ipsilateral perforant path stimulation. We examined input-output functions using a wide range of single pulse stimulation intensities and induction of LTP using high-frequency stimulation. In the 50-500 microA range of single pulse intensities, there were no significant differences among the diet groups in dentate gyrus evoked potentials. In response to high-frequency stimulation, prenatal ethanol-exposed rats showed a smaller increase in field EPSPs and population spikes compared with rats from either of the two control groups. Thus, prenatal exposure to moderate ethanol levels can produce a long-lasting deficit in synaptic enhancement in a neural pathway believed to be critical in certain forms of learning and memory. This deficit in hippocampal synaptic plasticity may, in part, account for cognitive impairments seen in children whose mothers consumed ethanol during pregnancy.

Analysis of Variance↗

PubMed1999

Effects of unilateral suckling on nursing behavior and c-fos activity in the caudal periaqueductal gray in rats.

In rats, suckling elicits kyphosis-the bilaterally symmetrical, upright, humpbacked nursing posture-and maximal expression of the immediate early gene c-fos in a region of the caudal periaqueductal gray (cPAG) that mediates the sensorimotor integration of kyphosis. We determined the effects of prepartum unilateral nipple removal on nursing behavior and c-fos expression during a 60-min mother-litter interaction on Day 7 postpartum. Compared with dams suckled by 6 pups bilaterally, dams suckled unilaterally displayed essentially normal maternal behaviors, including kyphosis. Unilaterally suckled dams, however, showed an increase in the abnormal prone nursing posture, a decrease in proportion of kyphotic nursing of total time over pups, and a 20% higher contralateral/ipsilateral ratio of cPAG neurons expressing c-fos. These results are consistent with an incompletely lateralized neural pathway conveying suckling stimulation to the cPAG and provide a mechanism whereby kyphosis is elicited by unilateral suckling when pups initiate nursing from their supine dam.

Animals↗

PubMed2000

Ovarian steroid action in the serotonin neural system of macaques.

The serotonin neural system plays an important role in cognitive, emotional and endocrine processes. If the ovarian hormones, oestrogen and progesterone, alter serotonin neural transmission, then functional changes in all of these systems would follow. Therefore, information on the effects of oestrogen and progesterone at a molecular level in the serotonin neural system was sought using non-human primates. Serotonin neurons express nuclear oestrogen receptor beta (ER beta) and progesterone receptors (PRs) which are gene transcription factors. Within serotonin neurons, the regulation of three genes related to serotonin neurotransmission was examined. The mRNA for tryptophan hydroxylase (TPH), the committal enzyme in serotonin synthesis, increased significantly with oestrogen treatment and remained elevated when progesterone was added to the oestrogen regimen. Serotonin reuptake transporter (SERT) mRNA decreased significantly with oestrogen treatment and addition of progesterone had no further effect. 5-HT1A autoreceptor mRNA decreased significantly with oestrogen treatment and addition of progesterone caused a further decrease. Little or no regulation of postsynaptic 5-HT1A, 5-HT2A or 5-HT2C receptor mRNAs was observed in hypothalamic target neurons. TPH protein is increased by oestrogen treatment and remains elevated with addition of progesterone in a manner similar to TPH mRNA. Medroxyprogesterone (MPA) blocked the stimulatory effect of oestrogen on TPH protein and tamoxifen reduced TPH protein levels below that observed in spayed monkeys. Together these data indicate that ovarian hormones and their synthetic analogues could modify cognitive and autonomic neural functions by acting on the serotonin neural pathway.

Animals↗

PubMed2001

Neural basis of novel and well-learned recognition memory in schizophrenia: a positron emission tomography study.

The level of familiarity of a given stimulus plays an important role in memory processing. Indeed, the novelty/familiarity of learned material has been proven to affect the pattern of activations during recognition memory tasks. We used visually presented words to investigate the neural basis of recognition memory for relatively novel and familiar stimuli in schizophrenia. Subjects were 34 healthy volunteers and 19 schizophrenia spectrum patients. Two experimental cognitive conditions were used: 1 week and again 1 day prior to the PET imaging subjects had to thoroughly learn a list of 18 words (well-learned memory). Subjects were also asked to learn another set of 18 words presented 1 min before the PET experiment (novel memory). During the PET session, subjects had to recognize the list of 18 words among 22 new (distractor) words. Subjects also performed a control task (reading words). A nonparametric randomization test and a statistical t-mapping method were used to determine between- and within-group differences. In patients the recognition of novel material produced relatively less flow in several frontal areas, superior temporal gyrus, insular cortex, and parahippocampal areas, and relatively higher activity in parietal areas, visual cortex, and cerebellum, compared to controls. No significant differences in flow were seen when comparing well-learned memory activations between groups. These results suggest that different neural pathways are engaged during novel recognition memory in patients with schizophrenia compared to healthy individuals. During recognition of novel material, patients failed to activate frontal/limbic regions, recruiting a set of posterior perceptual brain regions instead.

Adult↗

PubMed2001

Development of the gravity sensing system.

The utricle and saccule contain hair cells, which are the peripheral sensors of change in gravity that transmit signals regarding these changes to the neural components of the vestibular system. Although the fundamental neural pathways, especially the vestibular reflex pathways, have been investigated extensively, the principals underlying the functional development of this system are under study at present. The objective of this review is to identify the gravity-sensing components of the vestibular system and to present an overview of the research performed on their development. The second part of this review is focused on one important aspect of development, the emergence of electrical excitability using the chick tangential vestibular nucleus as a model. The importance of this research to understanding vestibular compensation and vestibular disturbance during spaceflight is considered. Because there is a conservation of the fundamental pathways and function in vertebrate phylogeny from birds through mammals, findings from studies on avians should contribute significantly to understanding the mechanisms operating in mammals. Also, we expect that as the events and basic mechanisms underlying normal vestibular development are revealed, these will provide practical tools to investigate the pattern of recovery from dysfunction of the vestibular system. This is related to the evidence suggesting that recovery of function in different systems and cell lines, including neurons, involves repeating certain patterns established during development.

Animals↗

PubMed2004

Antidepressants for smoking cessation.

BACKGROUND: There are at least two theoretical reasons to believe antidepressants might help in smoking cessation. Nicotine withdrawal may produce depressive symptoms or precipitate a major depressive episode and antidepressants may relieve these. Nicotine may have antidepressant effects that maintain smoking, and antidepressants may substitute for this effect. Alternatively, some antidepressants may have a specific effect on neural pathways underlying nicotine addiction, independent of their antidepressant effects. OBJECTIVES: The aim of this review is to assess the effect of antidepressant medications in aiding long-term smoking cessation. The medications include bupropion; doxepin; fluoxetine; imipramine; moclobemide; nortriptyline; paroxetine; sertraline, tryptophan and venlafaxine. SEARCH STRATEGY: We searched the Cochrane Tobacco Addiction Group trials register which includes trials indexed in MEDLINE, EMBASE, SciSearch and PsycINFO, and other reviews and meeting abstracts, in March 2004. SELECTION CRITERIA: We considered randomized trials comparing antidepressant medications to placebo or an alternative therapy for smoking cessation. We also included trials comparing different doses, using pharmacotherapy to prevent relapse or re-initiate smoking cessation and using pharmacotherapy to help smokers reduce cigarette consumption. We excluded trials with less than six months follow up. DATA COLLECTION AND ANALYSIS: We extracted data in duplicate on the type of study population, the nature of the pharmacotherapy, the outcome measures, method of randomization, and completeness of follow up. The main outcome measure was abstinence from smoking after at least six months follow up in patients smoking at baseline, expressed as an odds ratio (OR). We used the most rigorous definition of abstinence for each trial, and biochemically validated rates if available. Where appropriate, we performed meta-analysis using a fixed effect model. MAIN RESULTS: There was one trial of the monoamine oxidase inhibitor moclobemide, and one of the atypical antidepressant venlafaxine. Neither of these detected a significant long-term benefit. There were five trials of selective serotonin reuptake inhibitors; three of fluoxetine, one of sertraline and one of paroxetine. None of these detected significant effects, and there was no evidence of a significant benefit when results were pooled. There were 24 trials of bupropion and six trials of nortriptyline. When used as the sole pharmacotherapy, bupropion (19 trials, OR 2.06, 95% confidence intervals [CI] 1.77 to 2.40) and nortriptyline (four trials, OR 2.79, 95% CI 1.70 to 4.59) both doubled the odds of cessation. In one trial the combination of bupropion and nicotine patch produced slightly higher quit rates than patch alone, but this was not replicated in a second study. Two trials of extended therapy with bupropion to prevent relapse after initial cessation did not show a significant long-term benefit. There is a risk of about 1 in 1000 of seizures associated with bupropion use. Concerns that bupropion may increase suicide risk are currently unproven. REVIEWERS' CONCLUSIONS: The antidepressants bupropion and nortriptyline aid long term smoking cessation but selective serotonin reuptake inhibitors (e.g. fluoxetine) do not. The fact that only some forms of antidepressants aid cessation and that they do so regardless of depressive symptoms strongly suggests that their mode of action is independent of their antidepressant effect.

Anti-Anxiety Agents↗