Nicotine-alcohol interactions and attentional performance on an operant visual signal detection task in female rats

Nicotine and alcohol are very often co-used and co-abused. Thus, it is important to understand their interactions. In many ways, nicotine and alcohol have opposing effects. This can be clearly seen in terms of their effects on cognitive function. Nicotine effectively improves attention while alcohol impairs it. The current study was conducted to determine in a rat model the interaction of nicotine and alcohol on attention using an operant visual signal detection task. It is hypothesized that nicotine would reverse the alcohol-induced impairment in accuracy of performance in this task. Female Sprague-Dawley rats (N=35) were trained on a visual operant signal detection task for food reinforcement with 300 trials/session in three equal time blocks. The rats were divided into poor and good performers according to their predrug baseline performance accuracy. The first experiment examined the dose-effect function of alcohol (0, 0.375, and 0.75 g/kg i.p.) on this task. The lower alcohol dose significantly impaired percent correct rejection in the high-performing rats but not the low-performing rats. The higher alcohol dose significantly impaired percent hit performance during the first two thirds of the session in both high- and low-performing groups. The second experiment examined alcohol (0.75 g/kg i.p.) interactions with nicotine (0, 12.5, 25, and 50 microg/kg s.c.) on attentional performance. The 25 and 50 microg/kg nicotine doses caused a significant (P<.05) improvement in hit accuracy. Alcohol blocked this nicotine-induced improvement, even though at this later time it no longer had an effect of its own. In the high baseline group, the 25 microg/kg nicotine dose also caused a significant (P<.025) improvement in hit accuracy. As in Experiment 1, the high baseline group was not significantly impaired by 0.75 g/kg of alcohol. However, this alcohol dose did eliminate the nicotine-induced improvement. These results suggest that alcohol, when given alone, impairs sustained attention and blocks nicotine-induced attentional improvements even when it does not cause impairments on its own.     

Nicotinic-glutamatergic interactions and attentional performance on an operant visual signal detection task in female rats

Nicotinic systems have been shown to be critically involved in cognitive function including attention. Nicotine has been shown to improve performance on attentional tasks in humans with Alzheimer's disease, schizophrenia and attention deficit hyperactivity disorder. Nicotine has mixed effects on attentional accuracy in unimpaired rats with findings of increased, reduced or unaltered accuracy under different conditions. Nicotine effects on attentional function in rats might be more clearly seen in reversing impaired performance. The current study determined nicotine effects on attentional accuracy reduced by the NMDA receptor antagonist dizocilpine (MK-801). Sprague-Dawley rats (N=35) were trained on a food-motivated two-lever operant task with one lever correct after a brief visual signal (0.027-1.22 lx) for hits and the other lever correct after the absence of a signal for correct rejections. First, a dose response study of dizocilpine was conducted to determine the threshold for impairment. The rats were administered acute doses of dizocilpine (0, 12.5, 25 and 50 microg/kg, sc). The 50 microg/kg dose caused significant (p<0.0005) reduction in percent hit at the four highest signal intensities. Percent correct rejection was also significantly lowered by this dose (p<0.005). No effect was seen with 12.5 microg/kg and only minimal effect seen with 25 microg/kg. Then, nicotine-dizocilpine interactions were investigated. The rats were administered acute doses of dizocilpine (0, 37.5 and 50 microg/kg, sc) and nicotine (0, 25 and 50 microg/kg, sc), alone or in combination. Percent hit was affected by nicotine and dizocilpine in a complex fashion with only the nicotinexdizocilpinexsignal intensity interaction being significant (p<0.05). Percent correct rejection showed a more straightforward effect. Percent correct rejection was significantly reduced by 50 microg/kg dizocilpine (p<0.025). The addition of 25 microg/kg of nicotine significantly (p<0.025) reversed the dizocilpine-induced reduction of correct rejection. This study shows that dizocilpine reduces signal detection accuracy in a dose-dependent fashion. Nicotine can partially counteract an aspect of this reduction by reversing the dizocilpine-induced reduction of correct rejection.     

Nicotine-antipsychotic drug interactions and attentional performance in female rats

Schizophrenia is marked by pronounced cognitive impairments in addition to the hallmark psychotic symptoms like hallucinations. Antipsychotic drugs can effectively reduce these hallucinations; however, the drugs have not resolved the cognitive impairment. Interestingly, nicotine, a drug commonly self-administered by people with schizophrenia, has been shown to significantly improve cognitive function of people with schizophrenia. The current study was conducted to determine the effect of typical (haloperidol) and atypical (clozapine and risperidone) antipsychotic drug treatment on sustained attention in rats performing a visual signal detection task. In addition, the interaction of haloperidol with chronic nicotine administration was assessed. Female Sprague-Dawley rats were injected subcutaneously with clozapine (0, 0.6, 1.25 and 2.5 mg/kg), risperidone (0, 0.025, 0.05 and 0.1 mg/kg) or haloperidol (0, 0.01, 0.02 and 0.04 mg/kg). In the second part of the study, the interaction of acute haloperidol (0, 0.005, 0.01 and 0.02 mg/kg) and chronic nicotine (5 mg/kg/day, for 4 weeks via osmotic minipump) was characterized. Clozapine, risperidone and haloperidol all caused dose-related impairments in percent hit performance. There was a significant linear dose-related impairment in percent hit caused by risperidone. All the doses of clozapine caused a significant impairment in percent hit at the higher luminance intensities in the visual signal detection task. The 0.01 and 0.02 mg/kg haloperidol doses caused significant decreases in percent hit. The 0.04 mg/kg haloperidol dose impaired performance of the task to the point that reliable choice accuracy measurements could not be made. Chronic nicotine infusion significantly diminished the impairing effects of haloperidol on performance during weeks 1-2. In summary, both typical and atypical antipsychotic drugs significantly impaired sustained attention in rats. Haloperidol was more detrimental than clozapine and risperidone. Chronic nicotine diminished the adverse effects of haloperidol on performance. This study establishes a paradigm to reliably determine the attentional impairment caused by antipsychotic drugs.     

Effects of marihuana on auditory signal detection

23 male subjects were tested for auditory signal detection under a no-treatment condition, and smoke marihuana conditions containing 0, 50, 100 and 200 g ⁹-THC per kg body weight. Signal detection was measured under conditions of concentrated attention, in which the subject reported the presence or absence of a tone in a 3-sec noise burst; and divided attention, where the subject also repeated a series of six digits which were presented simultaneously with the noise burst. No differences were found between the no-treatment and placebo conditions. Significant dose-dependent impairment of signal detection resulted for the marihuana conditions under both concentrated and divided attention. Application of signal detection theory indicated that impaired performance was due to a decline in sensitivity (d), independent of changes in subject criteria (beta). There was also some indication of change in criteria—a greater tendency for erroneous reporting of a signal when it was not present.This work was supported by the National Highway Traffic Safety Administration DOT HS-150-2-236, the National Institute of Mental Health MH-17864 and K05-DA-70182, and the National Institute of Alcohol Abuse and Alcoholism AA-00251.     

Effects of nicotine and mecamylamine on cognition in rhesus monkeys

Rationale Nicotine and other agonists of nicotinic cholinergic receptors (nAChR) have been shown to improve performance in specific memory domains in rodents and monkeys. Such beneficial effects are observed in preclinical models of age-related cognitive decline, stimulating interest in nAChR ligands as possible therapeutics. Prior work has typically focused on assays of spatial working memory in rodent studies and visual recognition memory in monkey studies.Objective The current study was conducted to determine the role played by nAChRs in multiple types of memory in monkeys.Methods Rhesus monkeys (n=6) were trained to perform a battery of six behavioral tasks and then serially challenged with acute doses of nicotine (3.2–56 g/kg, IM) and the nAChR antagonist mecamylamine (0.32–1.78 mg/kg, IM).Results Nicotine improved performance on tests designed to assay visual recognition memory, spatial working memory and visuo-spatial associative memory, while mecamylamine impaired visuo-spatial associative memory. Ballistic and fine motor performance was not significantly improved by nicotine but fine motor performance was impaired by mecamylamine.Conclusions Although nicotine may improve performance in multiple domains, effects on visuo-spatial associative memory is the most specifically attributable to nAChR signaling.     

Selective immunolesioning of the basal forebrain cholinergic neurons in rats: effect on attention using the 5-choice serial reaction time task

Abstract Rationale. Excitotoxic lesions of the nucleus basalis magnocellularis (nbm) in rats produce deficits in performance of the 5-choice serial reaction time (5CSRT) task, suggesting that basal forebrain cholinergic projections to the neocortex play an important role in visuospatial attention. However, non-selective damage induced by excitotoxins may have confounded the interpretation of the specific contribution of the corticopetal cholinergic neurons of the nbm to attentional processes. Objective. The purpose of the present study was to produce selective immunolesions of the cholinergic neurons of the nbm in order to examine more precisely the role of the cholinergic projections of the basal forebrain on attentional performance in a 5CSRT task. Methods. Rats received bilateral injections of the selective cholinergic immunotoxin 192 IgG-saporin (0.067 μg/μl, 1 μl) into the nbm after baseline training in the 5CSRT task. Performance of sham and nbm lesion groups was then assessed during baseline and increased task difficulty conditions. Results. Contrary to results previously reported, accuracy of responding and behavioral inhibition were unaffected by the immunotoxin. Rats with nbm lesions showed, however, significant increases in omissions relative to control rats, most markedly during sessions with increased difficulty of signal detection, e.g., decreased stimulus intensity or duration. Magazine and correct latencies were unaffected, suggesting that the lesion-induced omissions were not due to changes in motivation. Omissions were highly correlated with percentage of choline acetylcholine transferase depletion. Reduced premature responses were also observed when the target stimulus was made less predictable. Conclusions. Although the 192 IgG-saporin lesion produced a different array of behavioral deficits than previously reported, these effects nevertheless are consistent with an important role of the basal forebrain cholinergic system in attentional function, in particular with accurate timing of stimulus presentation and target detection. Electronic Publication     

Improvement of performance on an attention task with chronic nicotine treatment in rats

Male, Holtzman rats were trained extensively on an attention task which required them to respond with a single lever-press to a very short, variably presented stimulus for food reinforcement, but which also required them to inhibit inappropriate responses. After performance had stabilized, two groups were treated with either nicotine base (100 g/kg, s.c., t.i.d.) or saline for 4 weeks. The groups were crossed-over so that the first received saline and the second nicotine for an additional 4 weeks. A 3-week saline recovery period followed. Rats were tested on the attention task daily through all periods. Analysis of the data indicated that independent of the treatment-order, rats performed more efficiently under nicotine treatment than under saline conditions. The improvement in performance was most notable in the reduction of inappropriate responding during chronic nicotine treatment. The significance of the behavioral changes in relation to proposed nicotine-induced neurophysiological changes and the two-arousal hypothesis are discussed.This work was supported by a Grant from the Council for Tobacco Research, U.S.A.Portions of the data in this paper were presented at the Meeting of the American Society for Pharmacology and Experimental Therapeutics, Burlington, Vt., August, 1971.     

Odor detection performance of rats followingd-amphetamine treatment: a signal detection analysis

The effects ofd-amphetamine sulfate (0.2, 0.4, 0.8, and 1.6 mg/kg SC) on the odor detection performance of 16 adult male Long Evans rats was assessed using high precision olfactometry and a go/no-go operant signal detection task. The drug or saline was administered every 3rd day in a counterbalanced order, with the injections occurring 5 min before each 260-trial test session. Relative to saline, enhanced detection performance to the target stimulus (ethyl acetate), as measured by a non-parametric signal detection index (SI), was observed following administration of 0.2 mg/kg of the drug, whereas decreased detection performance was observed following administration of 1.6 mg/kg of the drug. Significant increases in the responsivity index (RI) occurred at the higher drug dosages for the lower odorant concentrations. In addition, small but statistically significant increases in the latency to respond in the presence of the odor (i.e., S+ response latency) were present at the higher drug dosages. Overall, these data suggest that (a) odor detection performance is enhanced by low doses of amphetamine, (b) odor detection performance is depressed by moderate doses of amphetamine, and (c) drug-related alterations in response criteria occur following the administration of moderate doses of amphetamine.     

Dizocilpine-induced accuracy deficits in a visual signal detection task are not present following D-cycloserine administration in rats

The N-methyl-D-aspartate (NMDA) receptor system is thought to be underactive in schizophrenia which may contribute to attentional dysfunction in this disease. In a visual signal detection task that required discrimination of signaled-trials from trials with no signal, the NMDA receptor antagonist, dizocilpine (0.05 mg/kg), increased errors on non-signal trials. Co-administration of dizocilpine and 10.0 mg/kg D-cycloserine, a co-agonist at the glycine site on the NMDA receptor, significantly decreased the error rate on non-signal trials compared to dizocilpine alone. These results suggest that drugs targeting the glycine site may be beneficial for attenuating attentional deficits associated with an underactive NMDA receptor system.     

Characterisation of the effects of nicotine in the five-choice serial reaction time task in rats: antagonist studies

Rationale: Nicotine has been shown to decrease reaction time and increase anticipatory responses in a five-choice serial reaction time task (5-CSRTT) in rats, but the receptor mechanisms mediating this effect remain unknown. Objectives: To evaluate further the effects of nicotine in this task and to characterise the receptors mediating these effects. Methods: Using a standard 5-CSRTT protocol, rats were trained to respond to a 0.5-s visual stimulus, which was reduced to 0.25 s for experimental sessions to induce a performance decrement. The effects of acute (0.03–0.3 mg/kg IP) and repeated (0.1 and 0.3 mg/kg IP for 5 days) nicotine were studied, as was the ability of mecamylamine (1 mg/kg IP), hexamethonium (5 mg/kg IP), dihydro-β-erythroidine (6 mg/kg IP) and methyllycaconitine (10 mg/kg IP) to antagonise the effects of acute nicotine. Results: Nicotine had no effect on accuracy, but decreased response latencies, improved performance in the less-well attended stimulus locations and increased inappropriate responding after both acute and repeated treatment. The data suggest that nicotine improves readiness to respond and improves target scanning, and decreases the ability to withhold premature responses (i.e. increased impulsivity). Except for the reduction in error latency, all of the effects of nicotine were antagonised by the non-selective, centrally acting antagonist mecamylamine, whereas the peripheral antagonist hexamethonium had no effect, demonstrating that nicotine’s actions are central in origin. Dihydro-β-erythroidine, a competitive nicotinic antagonist, antagonised all of the effects of nicotine. In contrast, the α₇ antagonist methyllycaconitine had no significant effects against nicotine. Conclusions: These results demonstrate that the α₇ receptor subtype is not involved in the effects of nicotine in the 5-CSRTT and that its effects are more likely to be mediated by a receptor(s) such as α₄β₂, α₄β₄ and/or α₃β₂ which is sensitive to antagonism by dihydro-β-erythroidine. Received: 12 October 1999 / Final version: 9 December 1999     

Effects of acute nicotine on several operant behaviors in rats

The present experiment assessed nicotine's effects on complex cognitive processes using a variety of operant tasks in rats, including incremental repeated acquisition (IRA) to assess learning; conditioned position responding (CPR) to assess auditory, visual, and position discrimination; progressive ratio (PR) to assess motivation; temporal response differentiation (TRD) to assess timing; and differential reinforcement of low response rates (DRL) to assess timing and response inhibition. Acute nicotine administration (0.0, 0.3, 0.42, 0.56, 0.75, and 1.0 mg/kg, IP) increased IRA and CPR response rate without significantly altering accuracy. Nicotine had similar effects on response rate for PR. For TRD, nicotine had a U-shaped dose effect on accuracy, but failed to shift the mode of the TRD response distribution. For DRL, nicotine reduced accuracy and also shifted the mode of the DRL response initiation time distribution to the left. Nicotine produced an inverted U-shaped dose-effect curve for the overall number of "bursting" responses under both of these schedules. The results of this experiment suggest that nicotine can impair performance on some aspects of cognitive-behavioral performance, while simultaneously improving performance on others.     

Effects of acute and sub-chronic nicotine on impulsive choice in rats in a probabilistic delay-discounting task

Rationale

Cigarette smokers typically display impulsivity by preferring immediate rewards over larger, delayed rewards at shorter delays than do non-smokers. Suggesting causality, nicotine injections in rats increase the choice for an immediate reward over a larger, delayed reward.

Objectives

To examine the generality of this latter effect, the present study employed a delay-discounting task to determine if acute and sub-chronic nicotine will also increase impulsive choice when subjective reward value is manipulated by changes in the probability, rather than magnitude, of reward.

Materials and methods

Rats were presented with two levers, one of which delivered an immediate water reward on half of the trials, while the other lever delivered the same reward on every trial, but only after one of five increasing delays.

Results

Acute injections of 1.2 mg/kg, but not 0.8 mg/kg, of nicotine increased the preference for the immediate (but less certain) reward lever at intermediate delays. Moreover, twice-daily injections of 0.8 mg/kg of nicotine for 6 days progressively increased the preference for the immediate reward. Latency to make the first response on each trial was not affected by nicotine.

Conclusions

The similar increases in impulsive choice produced by both acute and sub-chronic nicotine in delay-discounting paradigms whether subjective reward value is manipulated by changes in reward magnitude or probability suggests that nicotine may be increasing what is common to these paradigms, namely delay discounting. Whatever the mechanism, these data indicate that both acute and sub-chronic nicotine may help develop and maintain an addiction by increasing impulsivity.     

Characterizing tolerance to trichloroethylene (TCE): effects of repeated inhalation of TCE on performance of a signal detection task in rats

Previous work showed that rats develop tolerance to the acute behavioral effects of trichloroethylene (TCE) on signal detection if they inhale TCE while performing the task and that this tolerance depends more upon learning than upon changes in metabolism of TCE. The present study sought to characterize this tolerance by assessing signal detection in rats during three phases of TCE exposures. Tolerance was induced in Phase 1 (daily 1-h test sessions concurrent with TCE exposure), extinguished in Phase 2 (daily tests in air with intermittent probe tests in TCE), and reinduced in Phase 3. Original induction in Phase 1 required 2 weeks, whereas reinduction in Phase 3 required less than 1 week. Tolerance persisted for 2 (accuracy) or 8 weeks [response time] in Phase 2 and was resistant to changes in test conditions in Phase 3. The slow induction, gradual extinction, savings during reinduction and lack of disruption from altered test conditions suggest mediation by instrumental learning processes. These data and most other evidence for behavioral tolerance to solvents can be explained by solvent-induced loss of reinforcement.     

Effects of systemic and intracerebroventricular administration of mecamylamine,a nicotinic cholinergic antagonist,on spatial memory in rats

The effects of both systemic and intracerebroventricular administration of mecamylamine, a nicotinic antagonist, were tested on the Morris water maze performance of rats. In experiment 1, mecamylamine (0, 3, and 10 mg/kg, IP) was administered before daily training sessions on the Morris water maze, a task in which rats use environmental cues to learn the location of an invisible escape platform in a large pool of water. The escape latencies of rats given the higher dose of mecamylamine were significantly longer than the latencies of rats given either saline or the peripherally-acting nicotinic antagonist hexamethonium (10 mg/kg). Analysis of search patterns during a free swim trial conducted in the absence of an escape platform confirmed the disruptive effects of the higher dose of mecamylamine. Similar drug effects were not observed when these rats were trained to a visible platform, and mecamylamine did not affect the retrieval of spatial information in well-trained rats. In experiment 2, similar effects were observed with ICV administration of mecamylamine (0, 10, 30, and 100 µg). The two higher doses increased escape latencies during the last day of place training and all three doses significantly impaired performance on a free swim. No significant effects were noted on subsequent training to a visible platform, and only the highest dose marginally impaired the retrieval of spatial information in well-trained animals. Thus, mecamylamine appears to impair the acquisition of spatial information in the Morris water maze but does not affect retrieval of previously acquired spatial information at comparable doses.     

Additive deficits in the choice accuracy of rats in the delayed non-matching to position task after cholinolytics and serotonergic lesions are non-mnemonic in nature

The role of serotonin (5-HT) and its interaction with the muscarinic or nicotinic receptor-mediated mechanisms in the modulation of working memory and motor activity was investigated by assessing the effects of 5-HT lesion and cholinergic receptor blockade on the performance of rats in a working memory (delayed non-matching to position, DNMTP) task. A global serotonergic lesion was induced by the intracerebroventricular adminstration of 5,7-dihydroxytryptamine (5,7-DHT). Post-mortem neurochemical analysis revealed that serotonin and 5-hydroxyindoleacetic acid (5-HIAA) levels were reduced in frontal and parieto-occipital cortices and in hippocampi of 5,7-DHT lesioned rats. 5-HIAA levels were also reduced in striatum. 5,7-DHT lesion slightly impaired choice accuracy of rats in the DNMTP task and also transiently reduced motor activity in rats. Even the lower dose of scopolamine (0.075 mg/kg), a muscarinic receptor antagonist, impaired the choice accuracy already at the shortest delay (i.e. not indicative of a working memory impairment per se), and caused a marked disruption of motor activity (lengthened response latencies, increased probability of omissions and decreased trials completed). Furthermore, the quaternary analogue, N-methylscopolamine (0.150 mg/kg), affected the motor activity of rats to the same extent as scopolamine. Mecamylamine (1.0; 3.0 mg/kg) also interfered with motor activity and it slightly decreased the choice accuracy, which was not dependent on the delay. Although mecamylamine disrupted the performance of rats in the DNMTP task, the disruption was not as severe as that seen with scopolamine. Moreover, both scopolamine and mecamylamine augmented the slight impairment on the choice accuracy of 5,7-DHT lesioned rats, but this was non-mnemonic in character. We conclude that there is no evidence for any major interaction between the serotonergic system and muscarinic or nicotinic cholinergic mechanisms in working memory per se, but muscarinic and nicotinic receptor antagonists may act additively with the 5,7-DHT lesion to disrupt the choice accuracy of rats. Received: 22 November 1995 / Final version: 25 November 1996     

Effects of acute and chronic nicotine on impulsive choice in rats

Impulsive choice, or preference for small immediate reinforcers over large delayed reinforcers, has been associated with cigarette smoking. The direct effects of nicotine on impulsive choice in laboratory animals are unknown. We examined the effects of acute and chronic nicotine injections, and the termination of injections, on impulsive choice in rats. Five rats made choices between a one- and a three-pellet reinforcer in a discrete trials procedure. The delay to the smaller reinforcer was always 1 s. A computer adjusted the delay to the larger reinforcer until the pattern of choices reflected indifference between the two alternatives. We assessed the effects of acute and chronic nicotine (vehicle, 0.03, 0.1, 0.3 and 1.0 mg/kg nicotine). The latency to make the first response of the session increased under the acute 1.0 mg/kg dose. There were no consistent differences in the effects of acute and chronic nicotine on response latency and lever pressing during the delays between choices. Acute injections of nicotine dose-dependently increased impulsive responding. After chronic injections, impulsive responding was increased equivalently regardless of dose, and it was increased even in the absence of nicotine. After drug injections were terminated, behavior remained impulsive for about 30 drug-free sessions, and then responding gradually returned to baseline levels. The results suggest that increases in impulsive choice were not due to anorectic effects, response biases or changes in conditioned reinforcement. Nicotine may have decreased the value of delayed reinforcers. Chronic nicotine exposure produced long-lasting but reversible increases in impulsive choice.     

Effects of weekly exposure to anatoxin-a and nicotine on operant performance of rats

This study examined the effects of acute and weekly administration of anatoxin-a and nicotine on operant performance. Anatoxin-a is a potent nicotinic receptor agonist produced by cyanobacteria, which are found in fresh waters throughout the world. Anatoxin-a is a potential human health hazard and has been responsible for numerous deaths of wildlife, livestock and domestic animals. Remarkably little is known, however, about the effects of anatoxin-a on behavior. Nicotine, the psychomotor stimulant in tobacco, has many well-documented behavioral effects, which often diminish (i.e. tolerance develops) when it is given daily. Male Long Evans rats initially were trained to respond under a multiple variable-ratio 30-response variable-interval 60-s (mult VR-30 VI 60-s) schedule of food reinforcement. They were then divided into 12 groups of 8 that received four weekly subcutaneous injections of anatoxin-a (0.05-0.2 mg/kg), nicotine (0.125-1.8 mg/kg), or vehicle 5-min prior to testing. When initially administered, each compound decreased response rates and reinforcement rates in both components of the multiple schedule. Substantial tolerance developed to the disruptive effects of nicotine with weekly administration. Tolerance also developed to the effects of anatoxin-a, although to a lesser degree; the highest dose severely decreased performance with little evidence of recovery. In conjunction with prior findings, these results suggest the behavioral effects of anatoxin-a and nicotine are similar, but not identical, and that relatively infrequent (episodic) administration can produce tolerance.     

Effects of nicotine on the acoustic startle reflex amplitude in rats

The acoustic startle reflex was used to measure changes in sensorimotor reactivity in response to nicotine administration and cessation. Male rats received saline, 6 mg/kg/day or 12 mg/kg/day nicotine delivered subcutaneously by osmotic minipumps. The pumps delivered their contents during a 10-day period of implantation, after which time they were explanted. Animals were tested for startle reflex amplitudes using two levels of white noise bursts prior to pump implantation, on days 1 and 7 of nicotine or saline administration, and on several days following drug cessation. Nicotine produced a dose-dependent increase in startle amplitude during the period of administration that decreased during cessation. Results are interpreted in terms of nicotine's actions to enhance attentional processes.This research was supported in part by USUHS protocol CO 7223. The views and opinions contained herein are the private ones of the authors and do not represent the opinions of the Uniformed Services University of the Health Sciences, the Department of Defense, or the Armed Forces Radiobiology Research Institute.     

The effects of caffeine and automaticity on a visual information processing task

The present study examined caffeine's effect on mental performance in contrast to a recent study (Loke and Goh, 1992) which examined the effects of caffeine user-effect on mental performance. Taken together, the studies would provide a detailed understanding of the effects of caffeine and automaticity on the visual search/detection domain of information processing. Analyses of the baseline measures of the visual search/detection task showed significant differences between low and high levels of automaticity and levels of task difficulty. Performance on the low difficulty level was higher than the high difficulty level, and performance on automatic task was higher than on non-automatic task. Caffeine, however, did not interact with automaticity and task difficulty. Therefore, given that the present study used unpractised (novice) subjects with similar levels of caffeine consumptions and personality characteristics, the visual search/detection domain of information processing is shown to be insensitive to the effects of caffeine. This supports the general view that caffeine does not affect cognition, learning, and memory performance. Also, the non-significant three-way interaction of drug, automaticity, and task difficulty would therefore suggest that caffeine does not affect resource capacity. Of note is that knowledge of drug administration assessments (drug guessing) was sensitive to the effects of caffeine in the automatic condition and not in the non-automatic condition, suggesting that the effects of caffeine are task-dependent. In contrast, the expected sensitivity of mood assessments to caffeine's effects was not shown. Since caffeine is shown to be a ‘weak’ stimulant, given its commonly known non-significant effects on mental performance, caffeine-administered subjects may lack sufficient external cues to allow them to perceive and report correctly that they were given caffeine.     

Attentional effects of nicotine and amphetamine in rats at different levels of motivation

Rationale The effects of drugs on performance of tasks used to assess attention might be confounded with changes in motivation. Few studies have investigated the role of motivational factors in such situations.Objectives To determine how changes in motivation for food influence performance of the 5-choice serial reaction time task and whether the effects of nicotine and amphetamine can be explained by motivational changes.Methods Male hooded Lister rats were trained to respond to a 1-s light stimulus presented randomly in one of five apertures in order to obtain food reinforcers. For three groups of rats (n=9–10), access to food was restricted to maintain body weights at 80, 90 or 95% of control weights. Saline and nicotine (0.025–0.2 mg/kg) were tested in each group, with and without pre-feeding (5 g). In a second experiment, saline and amphetamine (0.03–0.9 mg/kg s.c.) were tested without pre-feeding.Results High levels of motivation for food were associated with increases in anticipatory responses, fewer omission errors, shorter response latencies and completion of more trials, without change in accuracy. Nicotine, but not amphetamine, increased accuracy and the number of trials completed; whereas amphetamine, but not nicotine, increased omission errors. Both drugs decreased anticipatory responding at the largest doses tested. There were few interactions of motivational level with drug effects.Conclusions The improvements in performance produced by nicotine did not resemble the effect of increased motivation, but some effects of amphetamine resembled those of reducing the level of motivation for food. Motivational levels did not confound assessments of the attentional effects of the drugs in terms of response accuracy.