Biomedical subjects

A R Caggiula

Publications and source records attributed to A R Caggiula.

At least 37 records · Page 2Linked to original sources

PubMed1996

The effects of ethanol on striatal dopamine and frontal cortical D-[3H]aspartate efflux oscillate with repeated treatment. Relevance to individual differences in drug responsiveness.

Numerous inconsistencies in the reported effects of drugs that can be found in both the human clinical and animal experimental literatures have prompted attempts to identify the basis of this variability. Our data suggest that one source may derive from the tendency of many systems to oscillate in their response to repeated drug or stress exposure. In the first experiment a single administration of ethanol to male rats, either 2 or 30 minutes or 2 weeks before sacrifice suppressed amphetamine-induced dopamine efflux from striatal slices. However, when ethanol was given both 2 weeks and 30 minutes before sacrifice, the two treatments significantly attenuate each other's effects. In Experiment 2, the stress of a novel environment (black box) 30 minutes before sacrifice decreased fractional D-[3H]aspartate efflux from the medial frontal cortex. When a single injection of ethanol 1 week earlier was added to black box exposure, it depressed efflux still further. However, adding a third treatment (ethanol at 2 weeks and 1 week + black box at 30 minutes) significantly reversed the effects of the two treatments (ethanol + black box). When a four-treatment chain was used (ethanol at 3, 2, and 1 week + black box at 30 minutes), the attenuation of efflux was reinstated. These data complement other findings from this laboratory showing that repeated stress or drug exposure can lead to an oscillatory pattern of change in the effects of future exposures and, in this way, contribute to variability in drug responsiveness.

Amphetamine↗

PubMed1996

Oscillation follows drug sensitization: implications.

This paper begins with the question of whether physiological systems can sensitize indefinitely or whether, at some point, countervailing mechanisms are activated in the organism's attempt to maintain homeostasis. The question is addressed by the review and presentation of considerable data encompassing a host of systems showing that when they reach or approach their biological limits, unidirectional sensitization gives way to oscillation. The implications of this evolution to an oscillatory pattern of response are discussed with regard to cyclic disorders, addictive behavior, and the marked individual differences that characterize drug sensitization.

Animals↗

PubMed1995

Nicotine self-administration in rats.

Considering the importance of self-administration models in determining mechanisms of drug maintained behavior, we attempted to replicate the findings of nicotine self-administration by Corrigall and Coen. Male, Sprague-Dawley rats, trained on food reinforcement, acquired relatively high and stable rates of self-administration of IV nicotine bitartrate (0.03 mg/kg, free base). Extinction and reacquisition followed substituting saline and then nicotine, respectively. Responses, infusions and intake decreased at 0.003 mg/kg, while intake increased at 0.06 mg/kg. This model of nicotine self-administration provides a reliable alternative to experimenter-administration models for examining the effects of nicotine.

Animals↗

PubMed1995

Different methods of assessing nicotine-induced antinociception may engage different neural mechanisms.

Two methods were used to assess nicotine-induced antinociception: tail withdrawal from a hot water bath and hind paw withdrawal from a hotplate. Nicotine doses which produced 75-80% maximum response were 0.75 mg/kg (free base) for tail withdrawal and 0.35 mg/kg for paw withdrawal. The peripheral blocker chlorisondamine (0.1 mg/kg, SC) and the central antagonist, mecamylamine (1 mg/kg, SC) were each effective in blocking nicotine-induced increases in tail withdrawal latencies, suggesting that this effect of nicotine depends on either the action of nicotine at peripheral receptors or the functional integrity of those receptors. In contrast, nicotine-induced increases in paw withdrawal latencies were blocked by mecamylamine but not by chlorisondamine, even at other agonist/antagonist dose combinations. The results indicate that these two effects of nicotine involve at least partially separate pathways and may reflect a different mix of the antinociceptive and motor depressing effects of nicotine.

Analgesia↗

PubMed1995

Psychological stress and immunological responsiveness in normally cycling, follicular-stage women.

Nineteen women in the follicular stage of their menstrual cycles were assessed for immunological responsiveness to a 50-min series of three psychological tasks which reliably elicit cardiovascular and neuroendocrine stress responses. Ten follicular-stage women not subjected to stress served as controls. Stress decreased lymphocyte responsiveness to PHA and PWM, percent of CD4+ cells and the ratio of CD4+/CD8+ cells. Conversely, stress increased natural killer cell number and cytolytic activity, white blood cell, lymphocyte, T and B cell count. Except for natural killer cell number, none of these changes was exhibited by controls. Most of these stress responses are similar to those reported for men and form the basis for a continuing study of the effects of reproductive hormones and stress on cardiovascular and immunological function in women.

Adult↗

PubMed1995

Neurochemical and physiological effects of cocaine oscillate with sequential drug treatment: possibly a major factor in drug variability.

Variability in response to drug treatment is a poorly understood problem with severe consequences for both the individual and the health care delivery system. Our data suggest that one source of variability may be inherent in the way physiological systems normally respond to repeated drug exposures. We report that for a wide array of endpoints-amphetamine-evoked, in vitro striatal dopamine efflux, amphetamine and K(+)-evoked efflux of heart norepinephrine and nonevoked plasma levels of corticosterone and glucose-repeated, in vivo cocaine (15 mg/kg IP) administration to male rats precipitated successive oscillations in the magnitude or direction of the organism's responsiveness to subsequent cocaine administration. This capacity of cocaine to produce oscillations in response to successive administrations appears to be due to its foreign/stressful aspect rather than its specific pharmacological properties.

Amphetamine↗

PubMed1994

Immunological effects of acute and chronic nicotine administration in rats.

We previously demonstrated that acute nicotine administration decreased the response of rat blood leukocytes (PBL) to concanavalin A (ConA). We now extend those findings to a comparison between the effects of acute and prolonged nicotine exposure (ten daily injections), on PBL and splenocytes (SL). A single injection suppressed the PBL response to ConA and phytohemagglutinin (PHA); tolerance developed by ten injections. In contrast, acute nicotine did not affect SL response to ConA and reduced the PHA response only at the highest concentration. Ten nicotine injections enhanced SL responsiveness to PHA. The only change in PBL subsets was an increase in CD8+ cells following ten injections.

Animals↗

PubMed1994

Chronic and acute tolerance to subjective, behavioral and cardiovascular effects of nicotine in humans.

Understanding tolerance to effects of nicotine in humans may elucidate processes involved in the onset and maintenance of tobacco dependence. Subjective, behavioral and cardiovascular responses to nicotine were examined as a function of past history of nicotine exposure (i.e., smokers vs. nonsmokers, chronic tolerance) and of immediately preceding nicotine exposure (acute tolerance). Dose-effect relationships between nicotine (0-2 micrograms/kg via measured-dose nasal spray) and each response were determined in male and female smokers (n = 17) and nonsmokers (n = 18), with different doses presented on different days. Each day, subjects also received a challenge dose of 20 micrograms/kg 30 min after the previous dosing to assess acute tolerance. Plasma nicotine concentrations were 30% lower in nonsmokers compared with smokers and analyses were adjusted to control for this difference. Results showed significant changes in nearly all responses as a function of nicotine dose. Dose-effect curves were shifted to the right or dampened in smokers relative to nonsmokers for most subjective and some behavioral responses, consistent with chronic tolerance, but there was less evidence of chronic tolerance to other behavioral effects or to cardiovascular responses. A pattern of acute tolerance generally similar to that of chronic tolerance was observed across response domains (i.e., clear acute tolerance to subjective measures but less to behavioral or cardiovascular effects). These results support the notions that regular use of nicotine is associated with chronic functional tolerance and that repeated nicotine exposure during a single episode produces acute tolerance. A similar pattern of chronic vs. acute tolerance suggests similarity of mechanisms responsible for both "types" of tolerance. However, variability in tolerance magnitude across subjective, behavioral and cardiovascular response domains indicates that different mechanisms may be responsible for these different effects of nicotine.

Adult↗

PubMed1993

Acute stress or corticosterone administration reduces responsiveness to nicotine: implications for a mechanism of conditioned tolerance.

We have shown that conditioned tolerance develops to some of the behavioral and endocrine effects of nicotine in rats. Other investigators have suggested that tolerance to multiple nicotine injections in mice may be due, in part, to elevated plasma corticosterone (CORT) levels, since repeated nicotine injections are associated with elevated CORT, chronically elevated CORT reduces nicotine responsiveness and adrenalectomy disrupts nicotine tolerance. Three experiments tested the feasibility of this hypothesis, as a mechanism for conditioned nicotine tolerance in rats, by determining whether acute administration of CORT or manipulations that increase adrenocortical activity reduce nicotine responsiveness. In experiment 1, male rats were injected IP with CORT (1 mg/kg), vehicle (ETOH + distilled water) or no injection 10 min before nicotine (0.75 mg/kg, SC) and tested for nicotine-induced analgesia every other day for 10 days. A significant reduction in withdrawal latencies was obtained for CORT pretreated rats compared to animals given only nicotine. A similar reduction was produced by the vehicle pretreatment, which itself induced an elevation of endogenous CORT. Experiments 2 and 3 established that similar effects could be produced by doses of CORT as low as 0.125 mg/kg or by exposure to a novel environment which also elevated CORT levels. Results also suggest that a conditioned release of endogenous CORT was triggered by stimuli associated with nicotine delivery. These data are consistent with the hypothesis that a conditioned release of CORT could contribute to the development of tolerance to some of nicotine's effects.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

The effect of subjective and physiological arousal on dishabituation of salivation.

We have previously shown that salivation to the same food habituates, and recovers after presenting novel nontaste stimuli. This study assessed the effects of environmental stimuli that differentially influence subjective and autonomic arousal on dishabituation of salivation. Thirty female subjects were preloaded on a lemon yogurt milkshake and habituated to seven presentations of lemon juice. Prior to the eighth presentation of juice, subjects were presented an engaging video game designed to produce subjective but no autonomic arousal (LO), a video game plus mental arithmetic stressor, designed to produce both subjective and physiological arousal (HI), or a no stimuli (REST) control. Significant dishabituating effects of HI versus REST were shown for salivation. Heart rate was significantly higher during the dishabituator for HI than LO or REST conditions, which were equal. Finally, significant differences in arousal were shown between each of the three conditions. These results show salivation can be differentially dishabituated by nonfood stimuli, and these stimuli influence salivation without influencing subjective hunger or hedonics.

Adolescent↗

PubMed1992

Amphetamine or haloperidol 2 weeks earlier antagonized the plasma corticosterone response to amphetamine; evidence for the stressful/foreign nature of drugs.

We inquired whether a single exposure to amphetamine (AM) or haloperidol (HALO) could modify the plasma corticosterone (CORT) response to a second injection of AM 2 weeks later. Male rats were injected with 4 mg/kg d-AM sulfate and tested for water intake for 5 h before sacrifice. Overall, AM induced water intake but none of the pretreatments altered this effect. By contrast, preexposure to AM, HALO or its vehicle 2 weeks earlier prevented the elevation of plasma CORT obtained when AM was administered without pretreatment. A combined pretreatment of HALO or its vehicle with AM produced an even greater blockade of AM-induced CORT elevation. Manipulations which prevented AM-induced drinking reduced the effectiveness of AM pretreatment in attenuating AM-induced elevation in CORT, suggesting that the pretreatment may have been sensitizing the effectiveness of a coping response--drinking--in reducing the CORT effect. Our findings also indicate that a dopamine agonist (AM), a dopamine antagonist (HALO) and a nonspecific stressor (acidic vehicle) can all induce the same, long-lasting action on CORT. This strongly suggests that the effects of AM and HALO in this instance cannot be explained in terms of their pharmacological actions, which are opposite to one another, but instead relate to their properties as stressful/foreign agents to the organism.

Amphetamine↗

PubMed1992

One brief exposure to a psychological stressor induces long-lasting, time-dependent sensitization of both the cataleptic and neurochemical responses to haloperidol.

Rats were exposed for 10 minutes to one of several enclosures graded in novelty. In one experiment they were then simply sacrificed and plasma corticosterone determinations made in order to obtain an index of the relative stressfulness of these enclosures. In a second experiment the animals received haloperidol and were tested for catalepsy, 2 hours or two weeks following the novel experience. The most novel experience, exposure to a black box, resulted in the highest corticosterone levels and was the only one of our pre-treatments to induce significant enhancement of catalepsy as well as alteration of nucleus accumbens dopamine levels, 2 weeks--but not 2 hours--later. These findings indicate that brief exposure of adult animals to a psychological stressor can induce a long-term alteration in both behavioral and neurochemical responses to a drug and that this effect requires a minimum level of stress to get started and once triggered gets stronger with the passage of time.

Animals↗

PubMed1992

Habituation and dishabituation of human salivary response.

Habituation may be relevant for understanding how sensory stimuli influence factors related to ingestive behavior. In the first of three experiments in humans we showed that salivation and hedonic ratings to lemon or lime juice habituated within 10 presentations, and dishabituation of the salivation and hedonic ratings to the original juice were observed after a new juice was presented. Experiment 2 replicated the habituation and decrease in hedonics to lemon juice, and showed both dishabituation and a relative increase in hedonics when chocolate taste, rather than another juice, served as the dishabituating stimulus. In a third experiment we showed a video game, a nontaste stimulus, could serve as a distractor to prevent the development of habituation, as well as a dishabituator after habituation had occurred.

Adolescent↗

PubMed1992

Abstinence from smoking decreases habituation to food cues.

Smokers typically gain weight after cessation due, in part, to increased caloric intake. This increase may be due to enhanced responding to sensory characteristics of foods resulting from a failure to habituate to food cues. To test this possibility, salivation to eight presentations of strawberry yogurt was assessed in male smokers and nonsmokers in two sessions. To test stimulus specificity, on the ninth trial, subjects were presented either more strawberry yogurt or lemon yogurt. Smokers were studied under nonabstinent or abstinent conditions. Salivation for nonabstinent smokers and nonsmokers decreased over presentations, while abstinent smokers showed little change. Nonabstinent smokers and nonsmokers recovered salivation when the new flavor yogurt was presented, and showed greater consumption on the final trial for the different versus same flavor yogurt. Nonabstinent smokers participated in additional within-session smoking sessions to control for withdrawal. Nonabstinent subjects were not different across smoking or not smoking sessions, suggesting the effects are not due to the acute effects of withdrawal.

Adolescent↗

PubMed1992

Effect of food change on consumption, hedonics, and salivation.

This study assessed the influence of introducing a new food after repeated presentations of one food on food consumption, hedonics, and salivation. Male subjects were provided repeated 150-calorie courses of pizza or cheeseburger until satiety. Hedonics and salivation were measured before each course. Subject were then provided an additional 450 calorie course of the same or the new food. During the development of satiety, subjects showed reliable increases in fullness and decreases in hunger and hedonics. Salivation briefly increased to maximal salivation, followed by reliable decreases. No differences in pattern of change for fullness, hunger, hedonics or salivation were noted across foods. Presentation of the new food resulted in significantly greater caloric consumption than another serving of the same food (130 vs. 44.5 kcal), an increase in hedonics and salivation relative to presentation of the same food, with no influence on hunger or fullness. These results suggest that after satiety develops, response recovery for subjective, physiological, and behavioral components of eating can be observed when new, palatable foods are presented.

Adolescent↗

PubMed1992

Effects of nicotine on subjective arousal may be dependent on baseline subjective state.

The often disparate and contrasting effects of nicotine on subjective arousal in smokers may be due in part to differences in presmoking subjective state. In Study 1, on each of 2 days, 10 male smokers were divided into high- and low-baseline subgroups on the basis of median split of resting predrug baseline subjective arousal. Then, subjects received intermittent nicotine (15 mu/kg) or placebo via measured-dose nasal spray, with drug conditions counterbalanced between days. In Study 2, 32 male and female smokers were similarly divided into high- and low-baseline subgroups on subjective arousal prior to either smoking or sham-smoking (n = 16 each) during a single session. Results were virtually identical between studies in showing that subjective arousal responses to nicotine (Study 1) or smoking (Study 2) were significantly inversely related to baseline arousal level; those initially low in arousal showed large increases following nicotine or smoking whereas those high in arousal showed little change. No such baseline dependency of responses was seen following placebo or sham smoking. Baseline dependency of cardiovascular responses to nicotine or smoking was also evaluated in similar fashion to determine generalizability of these effects to nonsubjective responses. In each study, systolic blood pressure response was related to baseline level but there was no effect of baseline level on heart rate and diastolic blood pressure responses. Implications of these results for explaining differential rewarding effects of smoking are discussed.

Administration, Intranasal↗

PubMed1991

One experience with 'lower' or 'higher' intensity stressors, respectively enhances or diminishes responsiveness to haloperidol weeks later: implications for understanding drug variability.

This laboratory has previously shown that acute exposure to a variety of brief stressful events can have a very long-lasting influence on subsequent responsiveness to pharmacological and non-pharmacological stressors. In some cases the response to these agents is enhanced, while in others it is diminished: the common denominator being that in each instance the influence of the initial stressor grows stronger with the passage of time. Here, we identify one factor that determines which time-dependent effect is manifest. In 3 separate experiments, male rats were subjected to a single exposure to stressors of either lower or higher intensity and their effects on haloperidol-induced catalepsy and dopamine and dihydroxyphenylacetic acid levels in the nucleus accumbens and medial frontal cortex, measured either 1-2 h or 2 weeks later. The stressors were either environmental (needle jab or 1 h of immobilization), metabolic (200 or 750 mg/kg, i.p. of 2-deoxy-D-glucose), or no effect on haloperidol-induced catalepsy when stressors preceded such behavioral testing by 1-2 h. By contrast, when the interval was 2 weeks, the lower-intensity stressors all increased haloperidol catalepsy, whereas the higher-intensity stressors decreased the same response. In other words, a process that progressed with the passage of time was observed regardless of whether sensitization or diminution of haloperidol's action occurred. In contrast to the uniform bipolar behavioral effects observed, depending on the intensity of the prestressor, the neurochemical findings failed to show any evidence of bipolarity whatever.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dihydroxyphenylacetic Acid↗

PubMed1991

Behavioral economic analysis of smoking: money and food as alternatives.

The relative reinforcing value of smoking versus two nonpharmacological reinforcers, money and food, was evaluated in young female smokers in two experiments. In Experiment 1 eight smokers worked for access to smoking or money on concurrent progressive variable ratio schedules of reinforcement (VR4 to VR50) across two days of Smoking Deprivation or No Deprivation. During No Deprivation money was reliably chosen over smoking. During Deprivation subjects initially (VR4) chose smoking over money, but at subsequent comparisons allocated equal time to work for smoking or money. In Experiment 2 eight smokers were provided access to smoking or food across four conditions: No Deprivation, Smoking Deprivation, Food Deprivation and Smoking + Food Deprivation, using the same progressive variable ratio schedules as in Experiment 1. Results showed an increase in the reinforcing value of food after Food Deprivation and smoking after Smoking Deprivation. On the dual deprivation day, subjects initially (VR4) chose to work for food, showed equal preferences over the next three schedule comparisons (VR8-VR20), and from VR25-VR50 shifted their choice to smoking. An increase in percent of calories as fat was observed during all deprivation conditions. The results demonstrate the use of the concurrent schedule paradigm for assessing choice among pharmacological and nonpharmacological reinforcers, and shows the relative reinforcing value of smoking depends on recent deprivation, response demands to obtain the reinforcer and availability of alternative reinforcers.

Adolescent↗