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The modification by physostigmine of some effects of nicotine on barpressing behaviour of rats

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Article
Nicotine (0.16–0.50 mg/kg, SC) was found to exert a potent antinociceptive action on thermal stimuli as measured by the tail-flick test. This antinociceptive action of nicotine could be blocked by centrally active nicotinic or muscarinic blockers implicating both classes of cholinergic receptors in this effect. Quaternary blockers, however, failed to prevent nicotine-induced antinociception. This finding, together with the ability of small doses of nicotine (25 g) to induce potent antinociceptive effects when administered centrally, suggests a central site of action for the antinociceptive action of nicotine. The present results also support the suggestion that nicotine may selectively reduce sensitivity to certain classes of pain stimuli, perhaps through a central releasing action on acetylcholine.
Article
Nicotine's action on the central nervous system is complex and likely involves an interaction of neurotransmitters. To determine the time after administration of nicotine and dosage for neurochemical studies, locomotor activity of CD-1 mice was determined at 5 min intervals between 0-60 min. A low nicotine dosage (0.05 mg/kg) did not alter activity 5-15 min after drug injection, but increased activity 28% at 15-25 min post-injection. A high dosage (0.8 mg/kg) reduced total distance 62% and rearing 87% at 5-15 min; at 15-25 minutes total distance declined 56% and rearing 69%; all measures returned to control values after 30 minutes; rearing then increased at 40 min after nicotine. Pretreatment (15 min before nicotine) with mecamylamine (1.0 mg/kg), but not hexamethonium (1.0 mg/kg), prevented the depressant effect of nicotine. Dopamine (DA) and its metabolites as well as acetylcholine (ACh) synthesis were measured at the point of nicotine's maximal depressant action. Striatal levels of dihydroxyphenylacetic acid (DOPAC) were increased and ACh utilization was reduced in striatum (-25%) and cortex (-24%) 10 min after nicotine (0.8 mg/kg). Mecamylamine, while preventing the depressant effect of nicotine on locomotor activity, did not alter its effects on DA metabolism. These results demonstrate that the behavioral outcome of acute nicotine treatment is time and dose-dependent. Nicotine's depressant action appears not to be due to altered DA but may be related to changes in carbohydrate and acetylcholine metabolism.
Article
The effects of nicotine on bar-pressing behaviour in the rat are blocked by mecamylamine. The depressant phase of the effect is blocked by atropine, supporting the conclusion that this depression is mediated by released acetylcholine. The quaternary compounds chlorisondamine and atropine methylnitrate also antagonise the behavioural effects of nicotine but the doses required for this are far in excess of those which are effective peripherally, suggesting that the sites of interaction are central.
Article
1. Rats were injected with 0.8 mg nicotine/kg, 0.8 mg amphetamine/kg or with saline immediately before being tested for 30 min in activity boxes.2. During the first 3 trials the nicotine group were less active than the controls but from trial 5 onwards nicotine had a stimulant effect. The stimulant effect of the amphetamine did not alter with repeated injection.
Article
The social behaviour of rats of two laboratory strains was observed before and after the subcutaneous injection of nicotine. The dose, of 25 μg per kg, was about equivalent to that inhaled by a man smoking a cigarette.Paired male rats were separated daily, and observed once a week for 6 min after re-introduction. Acts and postures described by Grant & Mackintosh (1963) were recorded, and interpreted statistically by discriminant analysis and regression equations.There was a barely significant difference in the baseline observations between the randomly selected experimentals and controls. However, the difference was much greater after the administration of nicotine, was greater still after four daily injections, and fell to insignificance when nicotine was administered to the former controls, instead. The effects of nicotine therefore appear to be additive to differences between individual rats, and so were more clearly seen by considering the rats as their own controls.The greatest contribution to this effect of nicotine, in both albino and hooded rats, was a consistent reduction of aggression. In one observation, other behaviour involving approach to the other rat, investigation, sexual, and submission, was also slightly reduced; there was a little evidence that escape was marginally increased, and in one observation, a possible indication of nausea. The total activity of the rats was not consistently affected by nicotine.These other effects seemed insufficient to account for the reduction of aggression, and it was argued that, at a behavioural level, nicotine may have modulated this directly.
Article
Rats were trained to respond for water rewards on different bars in a Skinner box depending on whether they had previously been injected with nicotine or with saline. No other drug tested could consistently elicit responses on the nicotine correct bar. Pre-treatment with mecamylamine abolished the rats' ability to distinguish between nicotine and saline but pretreatment with chlorisondamine did not.
Article
The smoking behaviour of 36 subjects smoking cigarettes with different filter retention efficiencies for nicotine was studied. Subjects were observed while performing various tasks on a driving simulator and also during a resting period after the tasks. Smokers of cigarettes with high-retention filters took more frequent puffs and obtained nearly the same amount of nicotine as smokers of cigarettes with low-retention filters, both while performing the tasks and during the resting period. Smokers of both types of cigarettes took significantly more puffs and obtained more nicotine per unit time during the resting period than during the tasks. The results are compatible with the possibility that smokers automatically adjust the nicotine dose obtained from a cigarette to some "optimum" level which may vary with different activities.
Article
The effect of nicotine and total alkaloids extracted from smoke on the avoidance behavior of rats under extinction procedure has been measured in an experiment extended over a period of three months. There was no significant difference between the two substances, with both inhibiting the extinction of avoidance response to approximately the same degree. Significance against the control was achieved with all treatments, the effect being significantly greater with the dose of 0.2 mg/kg than with the two doses of 0.1 or 0.05 mg/kg.
Article
Rats of 3 strains were observed at regular intervals and their activity was recorded using four categories of behaviour-rearing, moving, grooming and immobile. Strain differences in control activity were found. Nicotine and physostigmine reduced the activity of the more active rats and increased that of the less active animals. Rearing behaviour was particularly susceptible to depression by both drugs. The similarity of effect of the two drugs supports the hypothesis that one of the actions of nicotine in the brain is the release of acetylcholine.
Article
1. The effects of small amounts of nicotine on electrocortical activity and central acetylcholine (ACh) release have been studied on anaesthetized cats.2. The most common effect of nicotine given intravenously in a dose of 2 mug/kg every 30 sec for 20 min was to cause desynchronization of the electrocorticogram, indicating cortical activation, and an increase in the release of cortical ACh.3. A larger dose given less frequently (4 mug/kg every min for 20 min) caused, in some experiments, an increase and in others a decrease in cortical activity. Such changes were accompanied respectively by an increase or decrease in cortical ACh output.4. The amounts of nicotine that affected the electrocorticogram and ACh release are probably similar to those absorbed by the cigarette smoker who inhales.5. The effects of nicotine on the electrocorticogram were transient, but the effects on ACh were prolonged. This suggests that at least two pathways are involved in the nicotine response.
Article
The effects of smoking deprivation and of smoking a single .8 mg, 1.3 mg or 2 mg nicotine yield cigarette, immediately post acquisition on a paired-associate learning task, were studied in 54 male smokers and 15 male nonsmokers. Subjects were retested for retention of the memorized material at intervals of one-half hour, one day, one week, and one month. Nonsmokers showed superior recall to all smokers at one-half-hour retest, and to some of the smoking groups on later re-tests. At one-month retest the low- and middle-nicotine cigarette smokers outperformed high-nicotine cigarette smokers. Low/middle-nicotine smokers achieved superior recall to nonsmokers at one-month retest. Results are discussed in terms of smoker versus nonsmoker differences, in terms of the effects of nicotine on memory consolidation, and in terms of the PAL response measure adopted.
Article
The effects of smoking a low (.7 mg) and a middle (1.3 mg) nicotine yield cigarette on paired-associate learning and retention under conditions of high and low intralist interference, and on serial learning and retention, were examined in groups of male undergraduate smokers (N = 24). The interaction between nicotine level and task difficulty in paired-associate learning was marginally significant. The 1.3-mg nicotine dose impeded learning under low interference conditions, but facilitated learning of high interference sets. Both nicotine levels significantly improved retention in paired-associate learning; task difficulty appearing to have little relevance. Serial learning data suggested that the effect is shown on long-term, rather than short-term memory.
Cigarette smoking is one of the most persistent habits known to man; for many years, he has been possessed by the bizarre but irresistible urge to inhale the smoke produced by burning the dried and shredded leaves of Nicotiana tabacum. The alternative methods of administration, sniffing and chewing, lost favor with the introduction of cheap cigarettes made from fluecured tobacco. Unlike the smoking of cigars and pipes, absorption of nicotine from cigarette smoke mainly takes place in the lungs. Despite convincing evidence that life is shortened by about 5 minutes for every cigarette smoked, consumption continues unabated throughout the world.
Article
During the last decade, nicotine has been used increasingly as an aid to smoking cessation and has been found to be a safe and efficacious treatment for the symptoms of nicotine withdrawal. This period has also seen significant advances in our understanding of the mechanisms underlying the psychopharmacological responses to nicotine, including, particularly, those that have been implicated in nicotine addiction. This paper reviews this decade of progress in the specific context of the therapeutic application of nicotine to the treatment of smoking cessation. Other putative future applications, particularly in the treatment of neurodegenerative disorders, are also reviewed.
Article
A single or repeated administration of nicotine in mice produced hyperactivity and conditioned place preference (CPP). Postsynapticdopamine (DA) receptor supersensitivity was also developed in nicotine-induced CPP mice. The hyperactivity induced by nicotine was evidenced by measuring the enhanced ambulatory activity using a tilting-type ambulometer. CPP effects were evaluated assessing the increased time spent by the mice to nicotine and the inhibition of CPP by the decreased time spent by the mice in the nonpreferred compartment. Postsynaptic DA receptor supersensitivity was evidenced by the enhanced response in ambulatory activity to the apomorphine, a DA receptor agonist. Administration of ginseng total saponin (GTS) prior to and during the nicotine treatment in mice inhibited not only nicotine-induced hyperactivity and CPP but also postsynaptic DA receptor supersensitivity in nicotine-induced CPP mice. These results suggest that inhibition by GTS of the nicotine-induced hyperactivity and CPP may be closely related with the inhibition of dopaminergic activation induced by nicotine and that the development of nicotine-induced CPP may be associated with the enhanced DA receptor supersensitivity. From these results, it is presumed that GTS may be useful for the prevention and therapy of these adverse actions of nicotine.
Article
With the assistance of two new associate editors, Alfred G. Gilman and George B. Koelle, the fifth edition retains the excellence set by previous editions of this classic text. To maintain the same overall length, several outmoded areas have been abbreviated or eliminated. There are discussions of many new drugs, as well as promising drugs whose availability in the United States is probable in the near future.The section on chemotherapy of neoplastic diseases has undergone extensive revision. The introductory section contains a very readable and informative discussion of pharmacokinetics, pharmacodynamics, and an interesting account of the process of development and approval of new drugs. The section on Parkinson disease has been extensively revised, with major emphasis on levodopa. The chapter on neurohumoral transmission and the autonomic nervous system remains the best source of information in this complex and rapidly changing area. The treatment of diuretics is completely up to
Article
Nicotine was administered subcutaneously to rats trained to press a bar for water rewards presented on variable-interval, fixed-interval, variable-ratio and fixed-ratio schedules. Nicotine had a biphasic effect, first depressing, then increasing response rates, except at the lowest dose tested (0.05 mg/kg) when the depressed phase was absent. Comparisons have been made with the stimulant drug amphetamine. Attention has been drawn to the importance of the relationship between dose and the time at which observations are made in the studies on the behavioural effects of nicotine.
Article
The effects of intraventricular injections of nicotine and the choline ester carbachol have been compared. Carbachol has two actions, one of which resembles that of nicotine. The nicotine-like actions are potentiated by cholinesterase inhibitors and prevented by hemicholinium in agreement with the hypothesis that nicotine acts by releasing acetylcholine.
The relative potencies of eserine and neostigmine were determined on three preparations of cholinesterase. Eserine was found to be twice as potent as neostigmine on the pseudocholinesterase of horse plasma, half as potent on the true cholinesterase of cat central nervous system, but twelve times as potent on the true cholinesterase prepared from the leech body wall. On the leech preparation, about ten times smaller concentrations of eserine than of neostigmine were required to potentiate the acetylcholine response, but after removal of the anticholinesterase from the bath fluid, the potentiation persisted much longer after neostigmine than after eserine. The greater sensitivity of the leech muscle to eserine is fully accounted for by the fact that its cholinesterase is more sensitive to eserine than to neostigmine. The longer lasting potentiation after neostigmine on the other hand suggests that this anticholinesterase becomes more firmly attached to the cholinesterase receptors in this muscle than does eserine.
Article
Several experiments indicated that a cholinergic system in the brain antagonizes a 2nd system, which activates behavior. Neuropharmacological considerations suggested certain drugs with which the activity of these systems could be altered. These experiments indicated that the cholinergic system acts selectively by preferentially antagonizing the effects of activation on unrewarded behavior. That is, there appears to be a cholinergic involvement in the mediation of the effects of nonreward. Although such interpretations are necessarily very tentative, there are inferential grounds for supposing that a cholinergic system selectively antagonizes the effect of activation on certain behavior and that the basis of this selectivity is the extent to which that behavior is unrewarded. (65 ref.)
Comparison of the effects of eserine and neostigmine on the leech muscle preparationEtude du conditonnement inhibiteur chez le rat Action de l'amph6tamine, de la chlorpromazine et des agents cholinergiques
  • B K Bhatracharya
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BHATrACHARYA, B. K.& FELDBERG, W. (1958). Comparison of the effects of eserine and neostigmine on the leech muscle preparation. Br. J. Pharmac. Chemother., 13, 151-155. 32 rINTERACTIONS OF NICOTINE AND PHYSOSTIGMINE 33 BOVET, D., ROBUSTELLI, F. & BIGNAMI, G. (1965). ]Etude du conditonnement inhibiteur chez le rat. Action de l'amph6tamine, de la chlorpromazine et des agents cholinergiques. Paris, 260, 4641-4645
The Pharmacological Basis of Therapeutics Effect of nicotine on operant behaviour of rats
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GOODMAN, L. S. & GILMAN, A. (1955). The Pharmacological Basis of Therapeutics. New York: Macmillan. HESS, W. R. (1954). In Diencephalon, Autonomic and Extrapyramidal Functions. New York: Grune & Stratton Inc. MORRISON, CATHLEEN F. (1967). Effect of nicotine on operant behaviour of rats. Int. J. Neuropharmac., 6, 229-240.
Cholinergic mechanisms in the control of behaviour by the brain
CARLTON, P. L. (1963). Cholinergic mechanisms in the control of behaviour by the brain. Psychol. Rev., 70, 19-39.
Étude du conditonnement inhibiteur chez le rat. Action de l'amphétamine, de la chlorpromazine et des agents cholinergiques
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