Ronald F. Mucha

Appetitive nature of drug cues confirmed with physiological measures in a model using pictures of smoking

Abstract. Rationale: In smokers, pictures of smoking that increase desire for a cigarette are described as pleasant rather than unpleasant. This suggests that these smoking cues may be appetitive and not withdrawal-like or aversive as held by traditional theories of drug cue formation. Objective: Cues for smoking were examined using physiological measures of motivational valence. Methods: Non-deprived smokers, deprived smokers and deprived smokers who expected to smoke (n=54) viewed a computer screen presenting experimental and control scenes (experiment 1). The acoustic startle reaction and activity of the corrugator and the zygomatic facial muscles were then measured after onset of smoking cues and standardized pleasant, neutral or unpleasant control scenes. Individuals who never smoked (n=18) were also used to test for cue effects on startle (experiment 2). Results: No evidence was found that smoking cues were aversive in smokers. The smoking cues affected the startle responses and corrugator activity in a way similar to that of pleasant control material but significantly different from that of unpleasant material; the cue effects on zygomatic activity was most similar to that of neutral material. The general pattern of effects was not influenced by overnight smoke deprivation, expectancy to smoke or smoke repletion, but it was different in never smokers where the smoking scenes were found to be similar to unpleasant control scenes. Conclusions: Non-subjective measures of motivational valence further suggest that drug cues are conditioned stimuli having appetitive effects. Startle response modulated by drug cues may be useful for probing motivational processes underlying dependence in the human.

Modulation of craving by cues having differential overlap with pharmacological effect : evidence for cue approach in smokers and social drinkers

Abstractu2002Rationale: An increased risk of drug intake produced by drug cues may reflect the fact that the cues are withdrawal-like or aversive, reflecting a conditioned adaptation to the drug’s acute effects. More recent work suggests that they may also be appetitive, signalling the goal characteristics of drug taking. Objective: These opposing mechanisms were tested in dependent smokers and in social drinkers by examining the motivational nature of drug cues that overlap differentially with the acute effects of the drug. Methods: Pictures of different phases of smoking or alcohol drinking were presented to deprived and non-deprived smokers, to never smokers and non-deprived smokers or to social drinkers. Desire for cigarettes or alcohol and momentary pleasure and arousal were measured after viewing an experimental picture or a pleasant, neutral or unpleasant control scene. Results: High desire for smoking was evoked by pictures of preparation for and actual smoking but not by scenes of the end of smoking, although the latter were best correlated with acute drug effect. This pattern was not affected by overnight smoke deprivation, it was seen in different smokers but not in never-smokers and it was replicated in social drinkers using pictures of alcohol consumption. Moreover, scenes evoking high desire to consume did not evoke states of momentary unpleasantness and they were seen as relaxing and not arousing. Control pictures had a minimal effect on desire to consume. Conclusions: In line with incentive models of drug cues, cues based on pictures of drug intake may be conditioned stimuli encoding cue approach and preparation for consumption.

Appetitive effects of drug cues modelled by pictures of the intake ritual: generality of cue-modulated startle examined with inpatient alcoholics

Abstract.Rationale: A cue-modulated startle test recently confirmed that smoking cues in smokers may not be withdrawal-like and aversive as traditionally believed. Objective: Analogous tests were applied to alcohol cues in inpatient alcoholics. Methods: Twenty-six withdrawn alcoholics (18 men) were examined. Alcohol-related pictures were compared to standardised pleasant, neutral or unpleasant control scenes using an acoustic startle test and measures of pleasure, arousal and desire for alcohol. Results: Pictures depicting preparation for drinking (cues) were different from unpleasant control pictures and similar to pleasant pictures but only on the startle test; no differential effects were found for alcohol craving and mixed motivational effects were reported subjectively. The effects were not due to arousal and control pictures depicting post-drinking events showed less effect than the alcohol cues. Conclusions: New techniques of measuring drug cue motivation indicate that drug cues may have incentive properties in individuals in treatment for alcoholism.

Pavlovian conditioning of opioid and nonopioid pain inhibitory mechanisms in humans

Learning processes such as respondent or Pavlovian conditioning are believed to play an important role in the development of chronic pain, however, their influence on the inhibition of pain has so far not been assessed in humans. The purpose of this study was the demonstration of Pavlovian conditioning of stress‐induced analgesia in humans and the determination of its opioid mediation. In a differential classical conditioning paradigm two different auditory stimuli served as conditioned stimuli and mental arithmetic plus white noise as unconditioned stimulus. Subsequent to four conditioning trials naloxone or placebo was applied in a double‐blind fashion on two test days. Both pain threshold and pain tolerance showed conditioned stress‐induced analgesia. Pain tolerance was affected by naloxone whereas pain threshold was not. The data of this study show that stress analgesia can be conditioned in humans and that it is at least partially mediated by the endogenous opioid system. Learning processes also influence pain inhibitory processes in humans and this effect might play a role in the development of chronic pain.

Abnormal affective responsiveness in attention-deficit/hyperactivity disorder: subtype differences.

BACKGROUNDnEmotional-motivational dysfunctions likely contribute to attention-deficit/hyperactivity disorder (ADHD), especially to hyperactive and impulsive symptoms. This study examined the affective modulation of the startle reflex in a large sample of ADHD patients. The aim was to compare subtypes of ADHD.nnnMETHODSnOne hundred ninety-seven unmedicated adult ADHD patients (127 combined type [ADHD-C]; 50 inattentive type [ADHD-I]; 20 hyperactive-impulsive type [ADHD-HI]) and 128 healthy control subjects were examined. The affect-modulated startle response as well as valence and arousal ratings were assessed for pleasant, neutral, and unpleasant picture stimuli.nnnRESULTSnControl subjects exhibited startle response attenuation and potentiation by pleasant and unpleasant pictures, respectively. In ADHD-HI, startle response was not attenuated by pleasant and not potentiated by unpleasant stimuli. In ADHD-C, startle response was not attenuated by pleasant pictures, and ADHD-I responded similar to control subjects but startle response was attenuated to a lesser degree by pleasant stimuli. The ADHD-HI group rated all pictures as more positive, and male ADHD-HI rated unpleasant stimuli as less arousing.nnnCONCLUSIONSnThis is the first study to assess the affect-modulated startle response in ADHD. It confirms emotional dysfunctions in these patients; all subtypes showed more or less diminished emotional reactions to pleasant stimuli. The hyperactive-impulsive type was also marked by blunted reactions to unpleasant stimuli. Results suggest that response patterns to emotional cues or reward may help to differentiate ADHD subtypes. Blunted emotional reactivity is especially pronounced in ADHD patients with symptoms of hyperactivity and impulsivity (ADHD-C, ADHD-HI).

The influence of low blood pressure and baroreceptor activity on pain responses.

The influence of baroreceptor modulation on pain perception has been extensively studied in normal and hypertensive subjects, but not in hypotensive subjects. The present experiment was performed to verify the following hypotheses: 1. Hypotensive subjects exhibit an increased pain response following baroreceptor activation compared to normals; 2. unlike the hypotensives, normal subjects, with normal baroreceptor reflexes, would learn to choose more often the baroreceptor activation condition compared to the opposite condition, during painful stimulation; 3. sensory and pain thresholds are correlated with blood pressure. The subjects (39 men), divided according to low and normal blood-pressure groups, participated in an experiment in which electrically-induced pain ratings and pain-evoked potentials were measured. Baroreceptor manipulation was performed by means of the PRES procedure. Whereas hypotensive subjects did not perceive any pain difference between the two baroreceptor conditions, activation and inhibition, normotensive men were able to perceive the baroreceptor activation condition as less painful. Similarly to subjective ratings, pain-evoked potentials of the low blood-pressure group showed a reversed trend compared to normals: larger somatosensory evoked potentials (N150-P260) to the baroreceptor activation condition and the opposite to the baroreceptor deactivation condition. Furthermore, results showed a negative correlation between diastolic blood pressure and sensory perception threshold, and a positive correlation between systolic pressure and pain threshold. Contrary to expectations, the rate of choice of baroreceptor conditions during painful stimulation did not show, in either group, any preference for baroreceptor activation.

Anxiogenic-like effects of opiate withdrawal seen in the fear-potentiated startle test, an interdisciplinary probe for drug-related motivational states

Abstract. Rationale: Anxiety-like effects may be universal to withdrawal from drugs of abuse. The study of withdrawal would benefit from the acoustic startle response (ASR), a discrete, cross-species reflex which is increased by fear-related states. However, existing reports of opiate-related effects on baseline ASR have not validated ASR as a measure of drug-related motivation. Objective: The effects of opiate treatment and withdrawal were examined using fear-potentiated startle, a startle test more sensitive to fear than baseline changes. Methods: Fear-conditioned rats were treated with Alzet osmotic pumps delivering 0.25xa0mg/kg per day fentanyl or placebo pumps. Experimentxa01 examined changes before and during opiate treatment on locomotor activity and baseline, prepulse inhibition, and fear-potentiated startle. Experimentxa02 examined the same responses during withdrawal precipitated after 4–7xa0days of treatment using IV naloxone. Results: Experimentxa01 revealed an attenuated fear-potentiated startle on the first test after the start of fentanyl treatment (4xa0h); this was not seen on subsequent tests and suggested tolerance to this acute effect. Experimentxa02 found an enhancement of fear-potentiated startle precipitated in fentanyl-treated rats after injection of 0.025 and 0.16xa0mg/kg naloxone; this was not seen at 1xa0mg/kg naloxone, even though more physical withdrawal signs were most prevalent at this dose. In neither experiment did locomotor activity, baseline ASR, or prepulse inhibition of the ASR show any treatment effect. Conclusions: Fear-potentiated startle may provide a specific and valid measure of anxiety-like effects of drug withdrawal. Discussed were conditions needed to see this effect and the relevance of the findings for different mechanisms of withdrawal discomfort.

Neural responses to BEGIN- and END-stimuli of the smoking ritual in nonsmokers, nondeprived smokers, and deprived smokers.

Drug-associated stimuli (cues) have a prominent role in addiction research because they are able to provoke craving and relapses. Generally, drug cues are seen as conditioned excitatory stimuli, which elicit drug seeking and usage. However, newer data suggest differential effects for smoking stimuli depending on their stage in the smoking ritual. Specifically, stimuli associated with the terminal stage of smoke consumption (END-stimuli) may evoke reactivity opposite to the reactivity evoked by stimuli associated with the beginning of smoke consumption (BEGIN-stimuli). This fMRI study compared 20 nondeprived smokers with 20 nonsmokers to unravel the influence of smoking-related pictures displaying the beginning (BEGIN-stimuli) and termination (END-stimuli) of the smoking ritual on neural activity in the addiction network. In addition, 20 deprived smokers (12u2009h deprivation) were investigated to explore the effects of deprivation on the processing of these stimuli. In nondeprived smokers, BEGIN-stimuli reliably activated the addiction network (for example, the ventral striatum, orbitofrontal cortex, and anterior cingulate cortex (ACC)). In contrast, END-stimuli triggered a differential pattern of activations as well as deactivations; deactivations were found in the ventral striatum and the ACC. Deprivation had no clear effect on the responses triggered by BEGIN-stimuli, but affected the reactivity to END-stimuli. Our data clearly suggest that stimuli associated with different stages of the smoking ritual trigger differential neuronal responses. While BEGIN-stimuli generally seem to activate the addiction network, END-stimuli presumably have some inhibitory properties. This new finding might add to a more differentiated understanding of cue reactivity and addiction.

Die Erfassung des Cravings bei Rauchern mit einer deutschen Version des “Questionnaire on Smoking Urges“ (QSU-G)

Zusammenfassung. Theoretischer Hintergrund: Der “Questionnaire on Smoking Urges“ (QSU) wurde von Tiffany und Drobes (1991) zur Einschatzung des Rauchverlangens entwickelt. Vergleichbare deutschsprachige Fragebogen fehlen. Fragestellung und Methode: Der QSU wurde ins Deutsche ubersetzt (QSU-G), und seine Faktorenstruktur, Reliabilitat und Validitat wurde an 129 Rauchern uberpruft. Ergebnisse: Eine Faktorenanalyse analog zu Tiffany und Drobes erbrachte eine gute Ubereinstimmung mit deren Zwei-Faktoren-Modell. Wie bei der englischen Fassung reprasentiert Skala 1 den Wunsch und die Absicht zu rauchen sowie die Erwartung positiver Auswirkungen des Rauchens. Skala 2 beschreibt die Erwartung einer Erleichterung von Nikotinentzugserscheinungen bzw. negativen Affekten und einen uberwaltigenden Drang zu rauchen. Beide Skalen waren reliabel (Cronbachs Alpha ≥ .87). Die Sensitivitat der Skalen fur Deprivations- und Rauchmanipulationen belegte ihre Validitat. Schlusfolgerung: Diese Befunde sprechen dafur, das Craving ...

Dependence on smoking and the acoustic startle response in healthy smokers.

Recent data from nicotine-dependent rats (14) and healthy smokers (18) would suggest that nicotine withdrawal modulates the acoustic startle reflex in a way similar to that of fear (5,20). We examined this directly using nonsmokers and healthy smokers who had no deprivation, brief deprivation (2-3 h), or prolonged deprivation (15 h). Groups differences in heart rate (HR), alveolar carbon monoxide (CO) levels, and desire and craving for cigarettes confirmed the presence of smoking withdrawal. However, there were no significant differences in the magnitude of the baseline startle response among the differently deprived smokers or between the smokers and the nonsmokers. Subsequent startle tests were carried out in the smokers during repeated sequences of preparing a cigarette for smoking (smoking cues) and then smoking. Whereas we did find statistically significant interactions of smoking deprivation with smoking cues and with renewed smoking, there was only weak confirmation of a priori predictions of motivational effects of smoking cues or of smoking. We conclude that smoking dependence may not affect the acoustic startle response itself; modulation seems to occur, but only after experience with the test situation. Discussed were possible mechanisms of this modulation in both humans and animals and further application of the startle response for providing interdisciplinary assessments of the motivational effects of nicotine withdrawal.