Chronic nicotine reverses working memory deficits caused by lesions of the fimbria or medial basalocortical projection.

Nicotine has been found in a variety of studies to improve performance in memory tasks. This study was conducted to determine if chronic nicotine administration is useful in counteracting the working memory deficits seen after lesions of the fimbria or the medial basalocortical projection. Rats were trained to asymptotic performance on a working memory version of the radial-arm maze. Then, they were given knife cut lesions of the fimbria or the medial basalocortical projection or underwent sham surgeries. At the time of surgery, rats in each treatment group were implanted with either nicotine-containing or placebo glass and Silastic pellets. Rats with fimbria or basalocortical lesions showed a significant decline in working memory performance. Chronic nicotine significantly improved choice accuracy in both lesioned and unlesioned rats. Nicotine treatment restored performance of the lesioned rats to control levels. These data show that in addition to improving memory performance in normal rats, nicotine can counteract lesion-induced memory impairments. Nicotine also may be useful for treatment of disease-related memory impairments such as seen in Alzheimer's disease.

Working memory performance and cholinergic effects in the ventral tegmental area and substantia nigra.

The nicotinic antagonist mecamylamine has been found to impair working memory performance in the radial-arm maze (RAM) after s.c. or i.c.v. administration. Mecamylamine has important interactions with dopaminergic (DA) systems. Mecamylamine-induced memory deficits in the RAM are potentiated by the D2 antagonist raclopride and reversed by the D2 agonist quinpirole. The nicotinic agonist nicotine has been found to improve working memory performance in the RAM after s.c. or i.c.v. administration. Nicotine-induced memory improvement in the RAM is potentiated by the D2 agonist quinpirole. The midbrain DA nuclei, the substantia nigra (SN) and the ventral tegmental area (VTA) have relatively dense concentrations of nicotinic receptors which may be critical sites of action for mecamylamine and nicotine. In the current study, the effects of mecamylamine (1, 3.3 and 10 micrograms/side) infusions into the SN (n = 12) and VTA (n = 13) on working memory in the radial-arm maze were examined in adult female Sprague-Dawley rats. The 10-micrograms/side dose of mecamylamine significantly impaired radial-arm maze working memory performance when infused into either the SN or VTA. No significant effects of mecamylamine on response latency were seen. The nicotinic agonists cytisine (0.1, 0.33 and 1.0 microgram/side) and nicotine (0.3, 1.0 and 3.3 micrograms/side) were administered in a counterbalanced order. The high dose of cytisine (1 microgram/side) nearly caused a significant deficit in choice accuracy. Nicotine slightly depressed choice accuracy but not significantly in this study. The interaction of nicotine and mecamylamine was then studied. A dose of 1.0 microgram/side of nicotine caused a significant decrease in choice accuracy. Interestingly, this was significantly reversed by a 3.3-micrograms/side dose of mecamylamine.(ABSTRACT TRUNCATED AT 250 WORDS)

Prenatal nicotine effects on memory in rats: pharmacological and behavioral challenges.

Cigarette smoking during pregnancy has been shown in a variety of studies to be associated with cognitive deficits in the children. Nicotine administration to rats during gestation has been found to cause subtle cognitive effects in the offspring. Some individual differences in cognitive impairment may be related to prenatal nicotine effects on noradrenergic (NE) systems. In the current study, 10 Sprague-Dawley rat dams were infused with approximately 2 mg/kg/day of nicotine ditartrate via osmotic minipumps and 10 control dams were exposed to vehicle-containing minipumps from gestational day (GD) 4-20. Starting on postnatal day (PND) 50, the offspring were tested for T-maze rewarded spatial alternation with intertrial intervals of 0, 10, 20, or 40 s. There was a sex- and delay-dependent effect of prenatal nicotine exposure on T-maze alternation. Nicotine-exposed males showed a significant deficit at the 0 s delay. In radial-arm maze (RAM) acquisition training there were no significant nicotine effects. However, significant nicotine-related effects were seen with subsequent behavioral and pharmacological challenges in the RAM. Changing the RAM testing location to an identical maze in a different room elicited a significant choice accuracy deficit in the prenatal nicotine-exposed rats compared with controls. Acute nicotine challenge did not cause any differential effects in the prenatal nicotine and control groups. During the isoproterenol (beta-NE agonist) challenge phase there appeared a significant facilitation of choice accuracy and speeding of response in the prenatal nicotine exposure group which was not seen in the control group. The alpha-NE agonist phenylpropanolamine caused a significant deficit in control females but not in the females prenatally exposed to nicotine. No differential effects of the alpha-NE antagonist phenoxybenzamine were seen in the prenatal nicotine and control groups. Throughout RAM testing there was a significant sex effect with males having better choice accuracy than females. These results demonstrate that the persisting cognitive effects of prenatal exposure to 2 mg/kg/day cause subtle effects in cognitive performance which can be elicited with behavioral and pharmacological challenge. These results also support previous studies suggesting the involvement of NE systems in persisting effects of prenatal nicotine exposure.

Intraneural ganglion: a case report with electron microscopic observations.

We report a case of common peroneal mononeuropathy caused by an intraneural ganglion in a 9-year-old boy. The mass and the contiguous nerve fascicles were excised under the operating microscope. Histologically, the cyst wall was composed of layers of elongated cells merging with fascicles that exhibited changes suggestive of a pressure-ischemia effect. Electron microscopy showed that the cells forming cyst wall were myofibroblasts, similar to the cells found in ganglia arising from joints elsewhere in the body. A review of the English literature on intraneural ganglia discloses 44 additional cases, of which 86% involved the common peroneal nerve. The most common clinical feature was motor dysfunction (followed by pain, sensory loss, and the presence of a palpable mass), and a significant male predominance is noted. The pathogenesis of this nerve lesion is discussed in light of our findings.

Chronic nicotinic stimulation and blockade effects on working memory.

Acute and chronic nicotine treatment has been found to improve learning and memory function in a variety of tasks. In several studies we have found that chronic nicotine infusion improves working memory performance. Replicating these results, the current study showed that chronic nicotine treatment (12mg/kg/day) significantly improved working memory performance in the radial-arm maze. The nicotine effect did not diminish during the 2 weeks following withdrawal. The nicotine-induced improvement was eliminated when the nicotinic antagonist mecamylamine (3mg/kg/day) was given concurrently, suggesting that the nicotine effect was mediated via actions on the nicotinic receptor. Surprisingly, when this chronic dose of mecamylamine was given alone, it caused a transient improvement in choice accuracy during the first week of administration. This improvement subsequently became attenuated and was not evident at all by the third and fourth weeks of administration.

Chronic nicotinic agonist and antagonist effects on T-maze alternation.

A variety of studies have found that nicotine improves working memory function. However, other studies have either not found improvements or have found nicotine-induced deficits. The demands of the particular memory test may be critical for the expression of the nicotine effects. In several studies, we have found that chronic nicotine administration improves working memory performance in the radial arm maze. Chronic mecamylamine coadministration reversed this effect. The current study was conducted to determine the effects of chronic nicotine and mecamylamine on choice accuracy in a T-maze spatial alternation task. The same dose and duration of nicotine administration that we have previously found to significantly improve choice accuracy in the radial-arm maze was not effective in altering T-maze spatial alternation. The critical difference in task demands may be the presence with T-maze alternation of proactive interference. During a session, a choice alternative repeatedly changes valence from correct to incorrect and back again. In contrast, with the radial-arm maze as run in our studies, in a session the valence of an arm only changes once from correct to incorrect. Previous work with nicotine effects on spatial alternation in an operant task found evidence that nicotine increased the negative effect of proactive interference on performance. In the current study, chronic mecamylamine caused a significant deficit in T-maze spatial alternation. This same dose did not produce a deficit in the radial-arm maze and, in fact, caused an improvement during the first week of administration.

Sertraline attenuates hyperphagia in rats following nicotine withdrawal.

Chronic nicotine administration can decrease food consumption and body weight. Abrupt withdrawal from nicotine can cause the reverse effect, hyperphagia and rapid weight gain. In the current study, the efficacy of sertraline, a serotonin reuptake inhibitor, on nicotine withdrawal-induced hyperphagia and rapid weight gain was assessed in rats. Sertraline was found to be effective in reversing the increase in feeding that occurred after withdrawal from chronic nicotine administration. Sertraline caused a dose-related decrease in food consumption in control rats not given nicotine. Doses of 5 and 10 mg/kg/day caused significant decreases while 2.5 mg/kg/day caused a slight though nonsignificant decrease in food consumption. Rats in which nicotine was abruptly withdrawn after 3 weeks of administration showed a significant increase in food consumption relative to controls. This increase was eliminated by the high dose of sertraline (10 mg/kg/day), but not by the lower two doses (2.5 and 5 mg/kg/day). Water consumption was affected in a similar fashion. Body weight gain was also affected by sertraline. During the first week after nicotine withdrawal, rats rapidly gained weight, but sertraline attenuated this. The 10-mg/kg dose of sertraline significantly attenuated the nicotine withdrawal-induced weight gain. These results suggest that sertraline can counteract the hyperphagia and rapid weight gain associated with nicotine withdrawal, and might therefore be a useful adjunct to smoking cessation.

Prenatal nicotine exposure and cognitive performance in rats.

In humans and animal models there is evidence that prenatal nicotine exposure causes lasting deficits in cognitive performance. The current study examined the cognitive effects of prenatal exposure of rats to 2 mg/kg/day of nicotine. This dose did not cause significant deficits in maternal weight gain, offspring litter size, or pup weight. The control offspring showed the normal ontogeny of spontaneous alternation from near chance (50%) performance to 80%-85% alternation. In contrast, the nicotine-exposed rats had the opposite progression with abnormally high alternation on days 22-30 and abnormally low alternation on days 35-52. Acquisition of choice accuracy performance on the radial-arm maze (RAM) was not altered in a major way by nicotine exposure. Minor nicotine-induced changes in choice accuracy were seen during the initial trials of acquisition. The nicotine exposed female offspring had a significantly longer response duration. Prenatal nicotine exposure did significantly alter the effects of subsequent drug challenges on choice accuracy performance. The nicotine-exposed male offspring were significantly more responsive to the amnestic effects of the nicotinic antagonist mecamylamine. In a subsequent challenge, the effects of the beta-adrenergic antagonist propranolol were examined. A significant dose-related impairment in choice accuracy was seen in the control rats. In contrast, the nicotine-exposed rats did not show any significant response to propranolol. This decreased responsiveness to adrenergic challenge parallels the reduction in adrenergic response to nicotine challenge we previously found in littermates to the rats of the current study. Prenatal nicotine exposure causes subtle alterations in cognitive performance that can be magnified by challenges of nicotinic and adrenergic systems.

Perineurioma (localized hypertrophic neuropathy).

Three patients with localized hypertrophic neuropathy ( LHN ) had a painless, slowly progressive mononeuropathy over many years, resulting in severe focal neurologic deficit. Grossly, the affected nerves showed a fusiform enlargement. Histologically, there was loss of nerve fibers, disorganization of the fascicular pattern, and proliferation of elongated cells with whorl formation. These cells exhibited no immunoreactivity for S-100 protein, and ultrastructural features set them apart from Schwann's cells. We conclude that LHN is not a disorder caused by hyperplasia of Schwann's cells but a benign peripheral nerve tumor of perineurial cell origin. This study also suggests that perineurial and Schwann's cells may not derive from the same precursor element.

Dysgraphia after right hemisphere stroke.

Acquired dysgraphia has been described as a disorder of graphemic selection and spatial temporal disorganization which can exist in isolation or as a component of a broader language or cognitive syndrome. There is little agreement on the locus of writing centers, although select areas within the left hemisphere have been suggested. We describe a patient who had dysgraphia after a right hemispheric stroke. He had no demonstrable signs of limb apraxia or visual field deficit, and only subtle signs of language impairment other than the writing disturbance. Treatment emphasized progressively more complex writing tasks which included the following: (1) written responses to picture/word stimuli, (2) word and sentence dictation, and (3) self-generated sentences and functional writing tasks. At discharge from the hospital the patient's writing was within normal limits. Our findings were similar to those described for a patient with a left hemispheric stroke who was primarily dysgraphic. We conclude that our patient's dysgraphia was a component of a subtle aphasia as well as a spatial temporal disorganization disorder.

Filamentous axonopathy in disulfiram neuropathy.

A 52-year-old female developed a sensorimotor polyneuropathy while on treatment with disulfiram. Electron microscopic examination of a sural nerve biopsy disclosed occasional axons distended by intermediate filaments. Identical changes can be induced in animals by carbon disulfide (CS2), a metabolite of disulfiram. Our findings suggest that disulfiram neurotoxicity is mediated by CS2 and is exerted on the distal axon.

Persistence of chronic nicotine-induced cognitive facilitation.

Nicotine has been found in a variety of species and behavioral paradigms to improve memory performance. The beneficial effect of nicotine has been seen after both acute and chronic administration. Interestingly, improved performance has been seen 24 h after acute injection and for at least 2 weeks after chronic administration. However, it is not clear from previous studies whether the persistence of the improved performance represents a true carryover of the drug effect or is due to the behavioral experience while under nicotine's effect. The current study was conducted to determine whether the facilitating effect of nicotine on learning and memory performance could be seen after withdrawal even if there was no behavioral training during the period of chronic nicotine administration. Rats were administered nicotine chronically for 3 weeks but were not tested during that time. Starting 1 week after withdrawal they were trained on a working memory paradigm in an eight-arm radial maze. The nicotine-treated rats started out at control-like levels of performance, but showed significantly faster learning as detected by three different measures of choice accuracy. By the final phase of testing the control subjects had caught up with the nicotine-treated rats. After the acquisition phase, acute challenges with the nicotinic and muscarinic antagonists, mecamylamine and scopolamine, did not elicit any differential effects in the nicotine-treated and control groups. The current study demonstrated that nicotine-induced cognitive facilitation persists for at least 4 weeks after withdrawal and does not depend upon behavioral test experience under the influence of the drug. The mechanism for this persisting effect is not currently understood.(ABSTRACT TRUNCATED AT 250 WORDS)

Patients' recollection of intensive care unit experience.

This study evaluates the recall of 100 patients after ICU admission. There was a wide spectrum of race, religion, occupation, and educational levels. The more common diagnoses included asthma, pneumonia, trauma, and adult respiratory distress syndrome. The average Acute Physiology and Chronic Health Evaluation (APACHE II) score was 12.3, and 68% of the patients were mechanically ventilated. The ICU atmosphere was described as friendly or relaxed by 94% of patients. Confidence in doctors and nurses was good. The most frequently reported unpleasant experiences were arterial blood gas sampling (48% of patients) and tracheal suctioning (30 of 68 ventilated patients). Only 6% of patients disliked ward rounds and discussion around the bedside. This study suggests that arterial lines or pulse oximetry could be used to avoid frequent arterial blood gas analyses and that tracheal suctioning should be performed with greater care. The need for better communication with patients is emphasized.