Biomedical subjects

J E Rose

Publications and source records attributed to J E Rose.

At least 19 recordsLinked to original sources

PubMed1992

Concurrent agonist-antagonist administration for the analysis and treatment of drug dependence.

Two key strategies for the treatment of drug dependence involve the use of agonists to substitute for the abused drug and the use of antagonists to block the reinforcing actions maintaining drug self-administration. A different strategy for the treatment of drug dependence is outlined, comprising the concurrent administration of an agonist and an antagonist. Concurrent administration of an agonist with an antagonist, in the proper ratio, should produce maximal occupancy of receptors and attenuation of the reinforcing actions of the abused drug. The addict would be relatively "insulated" from the reinforcing effects of the abused drug; at the same time the balance of agonist and antagonist effects is predicted to prevent withdrawal symptoms or intoxication resulting from an under- or over-stimulation of drug receptors. Advantages over the use of agonists alone and antagonists alone, and over mixed agonist-antagonist molecules, are discussed. Application of concurrent agonist-antagonist administration to the analysis of mechanisms underlying nondrug reinforcement and to the treatment of disorders involving receptor disregulation is also described.

Animals↗

PubMed1992

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)

Analysis of Variance↗

PubMed1991

The effects of smoking-related sensory cues on psychological stress.

Previous studies have shown that the sensory cues of cigarette smoking are important for smoking satisfaction and craving reduction. Sensory cues in the absence of pharmacological doses of nicotine have been found to be moderately satisfying and to reduce craving. The current study was conducted to determine if administration of the sensory cues of cigarette smoking with minimal nicotine would also provide relief from mild anxiety associated with anticipation of a difficult anagram test. This test has previously been shown to be sensitive to the anxiety relieving effects of cigarette smoking. Compared to the placebo control condition, the sensory condition caused a significant alleviation of the stress as measured by components of the Spielberger scale for anxiety. The addition of cigarette smoke containing 0.5 mg of nicotine to the sensory cues caused a slight though nonsignificant enhancement of the stress alleviation. These results demonstrate that sensory cues of smoking can provide similar effects as nicotine containing cigarettes with regard to stress alleviation. Previous studies had shown that sensory cues are important for the consumptive aspects of smoking (i.e., smoking satisfaction and craving reduction). The current study shows that sensory cues are important for other effects of smoking as well.

Adolescent↗

PubMed1991

Interactive effects of D1 and D2 agonists with scopolamine on radial-arm maze performance.

Pharmacological blockade of muscarinic cholinergic (ACh) receptors has been found to impair choice accuracy in a variety of tasks including the radial-arm maze. The cognitive impairment caused by the muscarinic antagonist scopolamine is reversed by the dopaminergic (DA) antagonist haloperidol as well as the selective D1 antagonist SCH 23390. In the current study, interactions were studied between scopolamine and selective agonists of D1 (SCH 38393) and D2 (quinpirole) receptors. Surprisingly, the D1 agonist SKF 38393 was found to significantly alleviate the scopolamine-induced choice accuracy deficit. In contrast, the D2 agonist quinpirole was not found to significantly alter the effects of scopolamine on choice accuracy but did have supra-additive effects of increasing choice latency. Both the D1 agonist SKF 38393 and the D1 antagonist SCH 23390 have been found to reverse the choice accuracy deficit caused by scopolamine and the deficit resulting from lesions of the medial projection from the basal forebrain to the cortex. Possible mechanisms for these effects are discussed.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

PubMed1991

Psychophysiological interactions between caffeine and nicotine.

The interactive effects of caffeine and nicotine were studied in twelve subjects. Mood and physiologic responses to the pharmacologic components nicotine and caffeine were measured, while controlling for the sensory/behavioral aspects of smoking and coffee drinking. Two experimental sessions presented a caffeine x nicotine design, with caffeinated or decaffeinated coffee followed at thirty-minute intervals by controlled inhalations of nicotine and nonnicotine smoke. Results showed that there was a significant interactive effect of caffeine and nicotine on subjective arousal such that nicotine decreased arousal only in the presence of caffeine. These findings extend previous work showing interactive effects of caffeine and self-titrated doses of cigarette smoke in affecting subjective arousal. The effects of nicotine on subjective arousal may, therefore, depend not only on nicotine dose, but also on the presence of caffeine. Heart rate was increased by nicotine and both systolic and diastolic blood pressures were elevated by caffeine. Caffeine also potentiated the increase in diastolic blood pressure resulting from smoke inhalations, but this occurred irrespective of nicotine dose.

Adult↗

PubMed1991

Nicotinic and muscarinic interactions and choice accuracy in the radial-arm maze.

Muscarinic acetylcholine (ACh) systems have long been known to be necessary for accurate performance in cognitive tests. Nicotinic ACh systems have been shown to be involved as well. However, there is only a limited amount of information concerning the interactions of these two branches of the ACh transmitter system. The current study was conducted to investigate the improvement in choice accuracy caused by muscarinic and nicotinic agonists and how it is affected by antagonists of these systems. Adult female Sprague-Dawley strain rats (N = 11) were trained on a working memory task in an 8-arm radial maze. Acute injections of the muscarinic and nicotinic agonists, pilocarpine (PILO, 1.0 mg/kg) and nicotine (NIC, 0.2 mg/kg), were made alone or in combination with the muscarinic and nicotinic antagonists, scopolamine (SCOP, 0.1 mg/kg) and mecamylamine (MEC, 10 mg/kg). NIC administration caused a significant improvement in choice accuracy compared with saline (p less than 0.01) and PILO caused a marginally significant improvement in choice accuracy (p less than 0.06). The combination of these nicotinic and muscarinic agonists did not cause an additive improvement. However, the improvement caused by either agonist was reversed by both nicotinic or muscarinic antagonists. This reversal was more complete for NIC than PILO despite the fact that NIC caused a greater improvement than PILO. These results suggest that muscarinic and nicotinic components of the ACh system, which are both important for cognitive function, interact in important ways. These interactions may be critical to consider when devising treatments for cognitive dysfunction associated with cholinergic hypofunction such as with Alzheimer's disease.

Animals↗

PubMed1991

Inter-relationships between conditioned and primary reinforcement in the maintenance of cigarette smoking.

Research on smoking cessation has increasingly focussed on pharmacological aspects of nicotine and nicotine withdrawal. However, cigarette smoking also provides a characteristic set of sensory cues. These sensory aspects of smoking are important to address in that they may be potent conditioned reinforcing stimuli linked to the actions of nicotine. The repetition of the smoking act thousands of times per year by a moderately heavy smoker leads to a strong conditioned association between the sensory aspects of smoking (the putative CS) and the pharmacological effects of nicotine (the putative UCS). Strategies for disrupting CS-UCS associations may be useful in developing more effective smoking cessation treatments. These include: counterconditioning of the CS; presenting the CS alone; presenting the CS with the UCS but pharmacologically blocking the UCS; and presenting the CS and UCS in an unconnected fashion. The role of sensory cues in alleviating craving for cigarettes is discussed, and specific techniques for duplicating relevant sensory aspects of smoking without delivering significant doses of nicotine are described. The combination of nicotine and nicotinic antagonists to block primary reinforcement and hasten extinction of conditioned reinforcement is also considered.

Arousal↗

PubMed1990

Biochemical and morphological differentiation of acetylcholinesterase-positive efferent fibers in the mouse cochlea.

We have compared the biochemical expression of cholinergic enzymes with the morphological differentiation of efferent nerve fibers and endings in the cochlea of the postnatally developing mouse. Choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) are present in the newborn cochlea at specific activities 63% and 25%, respectively, of their mature levels. The relative increases in ChAT, in AChE, and in its molecular forms over the newborn values start about day 4 and reach maturity by about day 10. The biochemical results correlate well with the massive presence of nerve fibers stained immunocytochemically for ChAT and AChE or enzymatically for AChE in the inner and outer hair cell regions. Ultrastructral studies, however, indicate the presence of only few vesiculated fibers and endings in the inner and outer hair cell regions. The appearance of large, cytologically mature endings occurs only toward the end of the third postnatal week. The discrepancy may be resolved in the electron microscopy using the enzymatic staining for AChE. Labeling is seen on many nonvesiculated fibers and endings in the hair cell regions, suggesting that the majority of the efferent fibers in the perinatal organ may be biochemically differentiated but morphologically immature. The results may imply that the efferents to inner and outer hair cells develop earlier than indicated by previous ultrastructral studies. Moreover, the pattern of development suggests that in the cochlea, as in other tissues, the biochemical differentiation of the efferent innervation may precede the morphological maturation.

Acetylcholinesterase↗

PubMed1990

Chronic nicotine and withdrawal effects on radial-arm maze performance in rats.

Rats were tested for choice accuracy in an eight-arm radial maze during and after chronic administration of nicotine via subcutaneously implanted glass and Silastic capsules. Nicotine administration significantly improved choice accuracy relative to controls. The effect gradually became apparent over the first 2 weeks of exposure and persisted through the third week. Surprisingly, the significant facilitation of the nicotine-treated rats relative to controls continued for 2 weeks after the end of nicotine administration. No effects of nicotine were seen on choice latency or the strategy to make adjacent arm entries.

Animals↗

PubMed1990

Cholinergic-dopaminergic interactions in cognitive performance.

Both acetylcholinergic (ACh) and dopaminergic (DA) systems have been found to be crucial for the maintenance of accurate cognitive performance. In a series of studies examining those aspects of cognitive function revealed by the radial-arm maze, we have found that these two neurotransmitter systems interact in a complex fashion. Choice accuracy deficits in the radial-arm maze can be induced by blockade of either muscarinic- or nicotinic-ACh receptors. The choice accuracy deficit induced by blockade of muscarinic receptors with scopolamine can be reversed by the DA receptor blocker, haloperidol. The specific DA D1 blocker SCH 23390 also has this effect, whereas the specific D2 blocker raclopride does not, implying that it is D1 blockade that is critical for reversing the scopolamine effect. On the other hand, the choice accuracy deficit induced by nicotinic blockade with mecamylamine is potentiated by haloperidol. This effect is also seen with the D2 antagonist raclopride, but not with the D1 antagonist SCH 23390, implying that it is the D2 receptor which is important for the potentiation of the mecamylamine effect. The relevance of the D2 receptor for nicotinic actions on cognitive function is emphasized by the finding that the selective D2 agonist LY 171555 reverses the choice accuracy deficit caused by mecamylamine. Nicotinic and muscarinic blockade are synergistic in the deficit they produce. Antagonist doses subthreshold when given alone produce a pronounced impairment when given together. This latter deficit can be reversed by the D2 agonist LY 171555. These studies have outlined the complex nature of ACh-DA interactions with regard to cognitive function. Possible neural circuits for these interactions are discussed. The effectiveness of these selective DA treatments in reversing cognitive deficits due to ACh underactivation suggests a novel approach to treating cognitive dysfunction in syndromes such as Alzheimer's disease.

Acetylcholine↗

PubMed1990

Characterization of the cognitive effects of combined muscarinic and nicotinic blockade.

Choice accuracy performance in the radial-arm maze is dependent upon the integrity of both the nicotinic and muscarinic cholinergic receptors. Pharmacological blockade of either of these subtypes of cholinergic receptors with mecamylamine or scopolamine impairs choice accuracy in the radial-arm maze. We have previously demonstrated that the performance deficit caused by muscarinic blockade is exacerbated in at least an additive fashion by coadministration of the nicotinic antagonist, mecamylamine. In the present study, it was found that mecamylamine and scopolamine act together in a greater than additive fashion in disrupting radial-arm maze choice accuracy. When doses of these drugs which do not by themselves cause significant impairments in choice accuracy are given together, they induce a pronounced impairment. Previous results have shown that the adverse effects of nicotinic blockade could be reversed by the dopaminergic D2 agonist LY 171555. In this study, this drug was found to attenuate the cognitive impairment caused by combined nicotinic and muscarinic blockade. On the other hand, the dopaminergic D1 antagonist SCH 23390 which has previously been shown to reverse the adverse effects of muscarinic blockade was not found in this study to attenuate the impairment of combined nicotinic and muscarinic blockade. Since combined nicotinic and muscarinic blockade approximates generalized cholinergic underactivation, treatments like LY 171555, which attenuate the adverse effects of this combined blockade, may be useful in treating syndromes like Alzheimer's disease, which are characterized by generalized cholinergic loss.

Animals↗

PubMed1990

The use of flavor in cigarette substitutes.

Cigarette smokers identify flavor as an important factor in the pleasure derived from smoking and for their choice of cigarette brand. The issue of cigarette flavor has received a great deal of study by cigarette manufacturers but relatively little by academic investigators. The paucity of literature is particularly acute in terms of the importance of flavor in cigarette substitutes, which are used to help people to reduce or quit smoking. In the current study, five different types of flavors added to a plastic cigarette substitute were assessed in experienced smokers. There were two menthol-like flavors and three tobacco-like flavors. Two groups of smokers were tested: menthol smokers and "regular" (non-menthol) smokers. Both types of smokers liked the two menthol flavors significantly more than placebo and rated the menthol flavors and the cigarette flavor as significantly more satisfying than placebo. Craving was differentially reduced in the two groups of smokers. Menthol smokers showed a small reduction in craving with the placebo, with a significant enhancement of this reduction seen with the addition of the "EZ Quit" menthol flavor.

Adult↗

PubMed1990

Development of a citric acid aerosol as a smoking cessation aid.

The satisfaction derived from smoking depends not only on the pharmacological effects of nicotine but also the sensory stimulation from smoke inhalation, particularly the tracheal 'scratch'. In a previous study, we found that a citric acid aerosol produces a tracheal 'scratch' and provides some of the same satisfaction as cigarette smoke. In the present study, we evaluated a new pocket-sized device for delivering a citric acid aerosol and examined some of the important variables for providing a satisfying substitute for cigarettes. In the first experiment, volunteers who smoked at least 10 cigarettes per day compared a citric acid aerosol (either alone or with flavor additives) to a cigarette and a placebo. The addition of cigarette smoke flavor was found to best enhance the satisfaction provided by the citric acid aerosol. In the second experiment, smokers were given compact citric acid inhalers to use throughout 8 h of cigarette deprivation. The degree of satisfaction was highly correlated with the intensity of throat sensation provided by the aerosol. This citric acid aerosol inhaler may provide a useful tool for smokers while trying to quit smoking.

Aerosols↗

PubMed1990

Low-nicotine regenerated smoke aerosol reduces desire for cigarettes.

We have developed a method of producing an aerosol with many of the sensory qualities of cigarette smoke, but with only 3% of the tar and nicotine and none of the carbon monoxide of a typical commercial cigarette. The aerosol was generated from a suspension of 1% cigarette smoke condensate in 10% ethanol. The aerosol, generated with an ultrasonic nebulizer, resembled smoke visually but had a larger particle size than cigarette smoke (3.5 microns vs. 0.5 micron mass median diameter). Twelve smokers rated blocks of 10 puffs of aerosolized smoke solution, a popular commercial cigarette, and an unlit cigarette (control). The blocks of puffs were evaluated for sensory qualities and smoking satisfaction obtained. The rated strength of the smoke aerosol was comparable to that of the commercial cigarette. The aerosol was rated significantly more desirable and more satisfying than the control, though not as desirable as the commercial cigarette. Surprisingly, the smoke aerosol reduced self-reported desire for cigarettes as much as the commercial cigarette. This new method is a promising approach for evaluating the role of sensory cues in smoking, and it may also be useful as a clinical tool for smoking cessation.

Adult↗

PubMed1990

Transdermal nicotine facilitates smoking cessation.

The efficacy of a transdermal nicotine patch in facilitation of smoking cessation was evaluated in a randomized double-blind trial. Sixty-five smokers who were highly dependent on cigarettes participated in the study, which included a behavioral smoking-cessation program. The rates of continuous abstinence were significantly higher in the nicotine group both initially (55% versus 34%) and at 3 weeks (18% versus 6%). Certain smoking withdrawal symptoms, including negative affect and hypoarousal, were effectively relieved by the nicotine patch. There was a trend toward a reduction in cigarette craving, whereas hunger and habit withdrawal symptoms were not affected. The main side effect associated with the nicotine patch was skin irritation. These findings suggest that a nicotine skin patch may be a useful aid to smoking cessation; however, the combination of other techniques with nicotine replacement may provide a more effective treatment for symptoms such as craving for cigarettes.

Administration, Cutaneous↗

PubMed1989

Mecamylamine increases nicotine preference and attenuates nicotine discrimination.

Eight subjects evaluated various qualities of cigarette smoke after being given a range of doses (0, 2.5, 10 and 20 mg) of the nicotinic receptor blocker mecamylamine. In one test condition, subjects were given either high or low nicotine tobacco smoke to determine the effects of mecamylamine on their subjective responses. In another test condition, subjects were allowed to adjust the nicotine dose level of the smoke to determine the effects of mecamylamine on dose preference. When the subjects evaluated puffs of smoke with high and low nicotine content, mecamylamine caused a dose-related decrease in the self-rated strength and harshness of the high nicotine dose level smoke. In contrast, there was little effect on the low dose smoke. At the highest mecamylamine dose (20 mg) there was no significant difference in the ratings of high and low nicotine cigarettes. Low doses of mecamylamine decreased the reported desire for a cigarette, and also attenuated the reduction in desire for a cigarette caused by smoking. When the subjects were allowed to select their preferred level of nicotine intake using a smoke mixing device, the 10 and 20 mg doses of mecamylamine caused a significant increase in self-administered nicotine dose level. Despite this compensatory increase in nicotine self-administration, the reduction in desire for a cigarette after smoking was still less than after placebo.

Adult↗

PubMed1989

Reversal of a mecamylamine-induced cognitive deficit with the D2 agonist, LY 171555.

Pharmacological blockade of either nicotinic or muscarinic cholinergic receptors has been found to impair choice accuracy in the radial-arm maze. Simultaneous blockade of both of these receptor types causes an additive impairment. However, despite these common effects, nicotinic and muscarinic receptors have been found to have differential involvement with dopamine receptors. The cognitive impairment caused by the muscarinic antagonist scopolamine is reversed by the D1 antagonist SCH 23390 but is unaffected by the D2 antagonist raclopride. In contrast, the cognitive impairment caused by the nicotinic antagonist mecamylamine is unaffected by SCH 23390 but is potentiated by raclopride. In the current study, the D2 agonist LY 171555 was found to be effective in reversing the radial-arm maze choice accuracy impairment caused by mecamylamine. In contrast, the D1 agonist SKF 38393 was not found to be effective. Thus, we have found selective dopaminergic D1 and D2 treatments which counteract the adverse cognitive effects of either nicotinic or muscarinic blockade. A combination of these treatments may be useful in treating the cognitive effects of generalized cholinergic underactivation.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

PubMed1989

Anxiolytic effects of smoking associated with four stressors.

There is a widespread belief that cigarette smoking alleviates stress. The literature reveals conflicting results on the anxiolytic effects of smoking. This study was designed to replicate a report that smoking (a) reduced subjective anxiety induced by stressful anagrams and (b) increased pain threshold for a cold pain task. This study (N = 15) included two other stressors: white noise and an auditory vigilance task. A significant Time x Condition (smoking vs. deprived) interaction was found for Spielberger State Anxiety Inventory scores in the anagram task. A borderline significant interaction effect was found for the cold pain task. No significant effects were found with the two other tasks. These results provide partial support for the popular notion that smoking mitigates stress-induced anxiety. No difference was found between the smoking and deprived conditions for either pain threshold or pain endurance.

Adaptation, Psychological↗