摘要:

AbstractNicotine has a wide variety of pharmacological effects. Some of these, such as improved attentiveness and memory, quickened reaction time, reduced appetite, and lessening of stress can be viewed as beneficial and may partially underlie tobacco use. They also suggest therapeutic uses of nicotine. Like any drug, nicotine has adverse effects as well, such as convulsant actions and cardiovascular effects. Also, like a variety of therapeutic drugs from caffeine to codeine, nicotine has the adverse potential to become habit forming or addictive. Many of the health damaging effects of tobacco use, such as cancer and lung disease, seem to result from compounds present in tar. Eliminating the more than 4,000 different compounds present in tar goes a long way in reducing adverse effects associated with nicotine intake. When developing nicotine for therapeutic use, it is critical to determine the mechanisms of its actions so that its beneficial effects can be maximized and its adverse effects can be minimized. This might be achieved with alternate routes of delivery of nicotine such as the skin patch or with novel nicotinic ligands currently under development. © 1994 Wiley‐Liss, I

ISSN:0272-4391    

DOI:10.1002/ddr.430310102

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

摘要:

AbstractData are reviewed, largely from experiments in the authors'laboratory, that suggest three modes of action of systemic nicotine in producing three different types of effect upon behavior and cognitive function. (1) Preexposure of a stimulus without consequence makes it harder subsequently to form associations to that stimulus, a form of selective attention known as latent inhibition. Latent inhibition is blocked by nicotine, an effect that is apparently mediated by a nicotine‐induced increase in dopamine release in the nucleus accumbens. (2) A single dose of nicotine proactively increases the partial reinforcement extinction effect measured several weeks later: that is, resistance to extinction is decreased by nicotine in animals that have been trained on a continuous reinforcement schedule, and increased in animals trained on a partial reinforcement schedule. This effect appears to be due to increased synthesis of tyrosine hydroxylase in the cell bodies of noradrenergic neurons in the locus coeruleus, followed by axonal transport to the hippocampus and increased synthesis and release of noradrenaline in that structure. (3) Nicotine improves vigilance in animals with cognitive deficits due to destruction of the forebrain cholinergic projection system, either as a consequence of excitotoxic lesions of the nuclei of origin of this system or after prolonged alcohol consumption; and also in human subjects with Alzheimer's disease (in which this system undergoes degeneration). This effect is most likely due to an action at denervated cholinergic synapses in the hippocampus and neocortex. © 1994 Wiley‐Liss,

ISSN:0272-4391    

DOI:10.1002/ddr.430310103

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

摘要:

AbstractIn rats, the effects of an intracerebroventricular (ICV) nicotinic agonist nicotine (NIC), the nicotinic antagonist mecamylamine (MEC), and combinations of NIC + MEC were assessed in a radial‐arm maze (RAM). In experiment 1, exploratory behavior was assessed in untrained rats (N = 13). The rats received 4 μg, 8.65 nmol NIC (NIC 4), 200 μg, 0.98 μmol MEC (MEC), and saline (SAL) ICV infusions. NIC 4 caused a significant increase in choice distribution compared to SAL (P<0.025). In experiment 2, rats (N = 10) were trained to perform a working memory task for food reinforcement in the RAM. ICV doses of SAL, NIC 4, NIC 8, MEC, MECNIC 4, and MECNIC 8 were administered after completion of the training period. MEC caused a significant deficit in choice accuracy when compared to SAL (P<0.025). This deficit was reversed when NIC 8 was coadministered with MEC (P<0.05). There were no significant effects on choice latency for either study. The effects of ICV NIC and MEC on RAM performance are generally similar to their systemic effects in that NIC improves and MEC impairs choice accuracy. The reversal of the MEC‐induced choice deficit by ICV NIC administration has not been reported with systemic administration. ICV MEC induces a choice accuracy deficit without increasing choice latency. This has not been seen with systemic MEC administration. The current result implies that the MEC‐induced choice accuracy deficit did not result from MEC‐induced sedation. The data indicate that previously reported changes in choice accuracy from peripherally administered NIC and MEC result from their central effects. © 1994 Wile

ISSN:0272-4391    

DOI:10.1002/ddr.430310104

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

摘要:

AbstractThe present study had two goals (1) to examine the effects of treatments with nicotinic agonist (nicotine) and antagonist (mecamylamine) on working memory in normal adult rats (14 months of age), and (2) to determine if treating aged (36 to 42 months of age), memory‐impaired rats with nicotine could improve their memory function. Memory testing was carried out using a delayed non‐matching to position paradigm in a T‐maze. Rats were trained to run down one arm of the maze (e.g., right) on an information run and then, after a variable memory delay period of 10, 90, or 180 sec, run down the other arm (e.g., left). In normal adult rats after water injection, memory accuracy was inversely related to memory delay (>90, 75, and 67% accuracy at the 10, 90, and 180 sec delays, respectively). Administration of nicotine (0.1 or 0.4 mg/kg), or mecamylamine (2.5 or 5 mg/kg), or combinations of these drugs had no significant effects on memory in these rats. However, mecamylamine alone or in combination with nicotine reduced running speed in the T‐maze in normal adults, indicating that the drugs did produce some behavioral effects. In aged rats, memory accuracy after water injection was much lower than that of younger adults, averaging 64, 57, and 50% at 10, 90, and 180 sec delays. Interestingly, nicotine injections of 0.1 or 0.4 mg/kg resulted in highly significantly improved accuracy in the memory task. The deficit in memory accuracy in aged rats, evident even at the shortest delay period (10 sec), suggests that the rats may have had impairments in attention or visual discriminatory ability. If this is so, then the beneficial effects of nicotine observed in this study may be more related to its effects on attention rather than memory directly. © 1994 Wiley

ISSN:0272-4391    

DOI:10.1002/ddr.430310105

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

摘要:

AbstractNicotine has been found to improve memory performance in a variety of tests including the radial‐arm maze. Nicotine may have effects mediated by promoting the release of dopamine. The present study was conducted to determine the interactions of nicotine with D1and D2agonists. Rats were acutely administered nicotine, the D1agonist SKF 38393, and D2/D3agonist quinpirole, and nicotine together with each of these agonists. Nicotine significantly improved choice accuracy in the radial‐arm maze. The D1agonist SKF 38393 significantly impaired choice accuracy. Nicotine was effective in reversing this effect. The D2/D3agonist quinpirole showed a trend toward potentiating the improvement in choice accuracy caused by 0.2 mg/kg (0.43 μmol/kg) of nicotine. These data show that, as with the nicotinic antagonist mecamylamine, there are significant interactions of dopamine systems with nicotine effects. © 1994 Wiley‐Li

ISSN:0272-4391    

DOI:10.1002/ddr.430310106

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

摘要:

AbstractThe effect of the benzodiazepine‐receptor antagonist flumazenil on the facilitatory effect of (−)‐nicotine on memory in septal‐lesioned rats in a spatial task and in the inhibitory avoidance test in mice was investigated. In the two‐platform spatial discrimination test, septallesioned rats exhibited a significant number of errors in comparison to sham animals, an effect that can be reversed by the administration of (−)‐nicotine during the training phase. Flumazenil did not affect the performance of septal‐lesioned rats but it blocked the facilitatory effect of (–)‐nicotine on lesioned rats. In the inhibitory avoidance test in mice,(−)‐nicotine as well as flumazenil facilitated retention of the test at 0.62 and 10 μmol/kg, respectively. However, a low‐noneffective dose of flumazenil blocked the memory enhancing effect of (−)‐nicotine. The blockade of the facilitatory effect of (−)‐nicotine by flumazenil in normal and septal‐lesioned animals suggests that the cognitive effect of (−)‐nicotine requires the activation of benzodia

ISSN:0272-4391    

DOI:10.1002/ddr.430310107

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

摘要:

AbstractThe purpose of the present study was to determine the possible role of cholinergic mechanisms in the anticonflict effects of the anxiolytic diazepam. Male Sprague‐Dawley rats were tested with a modified Geller‐Seifter procedure using a multiple reinforcement schedule in which unpunished responding in one component was reinforced according to a fixed‐interval 60‐sec schedule, and punished responding in the other component resulted in both food and a brief electric shock presentation according to a fixed‐ratio 1 schedule. In Experiment 1 (−)‐nicotine antagonized the increase in punished responding that was produced by diazepam. In Experiment 2 diazepam produced selective increases in punished responding that again was antagonized by (−)‐nicotine, a nicotinic cholinergic agonist, whereas arecoline, a muscarinic cholinergic agonist, did not antagonize diazepam's increase in punished responding. Neither drug produced any significant changes in unpunished responding. In Experiment 3 it was shown that the centrally acting nicotinic antagonist, mecamylamine, was able to block nicotine's antagonism of diazepam. These results suggest that there is an interaction between central nicotinic cholinergic mechanisms and diazepam's anticonflict effects in this animal model for anxiolytics, and support clinical observations that smoking can reduce some effects of benzodiazepines. © 19

ISSN:0272-4391    

DOI:10.1002/ddr.430310108

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

摘要:

AbstractAlthough lobeline and nicotine are both potent ligands at neuronal nicotinic cholinergic receptors, chronic lobeline does not produce the upregulation of nicotinic receptors found with chronic nicotine or the less potent agonist anabasine. Since agonist‐induced receptor upregulation is believed to result from receptor desensitization during chronic treatment, this suggests that lobeline may not desensitize neuronal nicotinic receptors. We addressed this question by comparing lobeline‐ and nicotine‐induced desensitization of the actions of nicotine, using body temperature and locomotor activity as dependent variables. Nicotine pretreatment reduced the hypothermia and locomotor suppression produced by a subsequent nicotine challenge, whereas lobeline pretreatment did not. When tested alone, both nicotine and lobeline reduced locomotor activity and body temperature to a similar degree, but lobeline was significantly less potent. The reductions in activity and temperature produced by nicotine were significantly attenuated in chlorisondamine‐treated mice, whereas treatment with this long‐lasting nicotinic cholinergic antagonist did not alter the effects of lobeline. Thus, nicotine and lobeline appear to differ in their ability to produce desensitization. Furthermore, the effects of these two compounds on locomotor activity and body temperature may be mediated via different mechanisma. © 1994 Wiley

ISSN:0272-4391    

DOI:10.1002/ddr.430310109

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

摘要:

AbstractFour‐day food intake reports, collected with electronic diaries, and saliva probes for cotinine analysis were obtained from 39 smokers and 43 nonsmokers. The nonsmokers had a higher caloric intake than the smokers, but this was related to more frequent sport activities. The distribution of energy intake across carbohydrates, fat, and protein was identical for both groups, but the smokers consumed bread, sweets and desserts, cheese, fruit juices, muesli (a cereal and yoghurt mixture), and water less frequently, but also more soft drinks, coffee, and alcohol. Only coffee and alcohol drinking were correlated with saliva continine. For two additional days, the recording of food intake was continued together with the continuous recording of activity and heart rate, intermittent measurements of blood pressure, assessments of subjective state, and performing a mental task. On one of these 2 days, the smokers had to abstain from smoking. Abstinence lowered heart rate and increased caloric intake by about 500 kcal, whereas actometer readings, blood pressure, subjective state, and mental performance were unaffected. Also unaffected were the percentage intake of fat, protein, and carbohydrates and the frequency of consuming particular food items. Post hoc correlations between subjective state, cotinine measures, excess intakes of total calories, macronutrients, and specific groups of food items were obtained only occasionally and in an inconsistent fashion. It is suggested that effects of smoking on taste and eating as a hedonic substitute when abstaining might represent important factors for food intake beyond the effects of nicotine. The new methods developed for this study appear to offer a way to obtain detailed information under particularly naturalistic conditions in studies on smoking and related problems. © 1994 Wiley‐Liss,

ISSN:0272-4391    

DOI:10.1002/ddr.430310110

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

摘要:

AbstractThe loss of central nicotinic receptors is a neurochemical hallmark of several degenerative brain disorders, notably Alzheimer's disease (AD) and Parkinson's disease (PD). However, uncertainty has remained about the significance of this loss for the cognitive symptomatology of these disorders. Symptoms of impaired acquisition of information and short‐term storage, impaired memory consolidation, attention, visual perception, and speed may reflect nicotinic lesions. Administration of the nicotinic antagonist mecamylamine in young and elderly humans produces significant dose‐related impairment of new learning, liberalization of response bias, and slowing of reaction time. These results suggest that mecamylamine may in part model the results of nicotinic receptor loss in AD and that nicotinic augmentation of some aspects of cognitive functioning may be a worthwhile strategy to pursue, particularly if agents can be developed that are more selective than nicotine itself. © 1994 Wiley‐Lis

ISSN:0272-4391    

DOI:10.1002/ddr.430310111

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY