Heavy marijuana use but not deprivation is associated with increased stressor reactivity.

Although stressors appear to motivate marijuana use, and marijuana use, in turn, is believed to induce stress system neuroadaptations, relatively little empirical work has explicitly tested for stress neuroadaptations associated with heavy marijuana use. We examined stressor reactivity to threat of unpredictable electric shock via startle potentiation among heavy marijuana users and a control group that reported minimal history of marijuana use. Heavy marijuana users were randomly assigned to 3 days of marijuana deprivation or no deprivation. This design allowed us to test contrasts for heavy (vs. minimal) use and deprivation (vs. no deprivation) on stressor reactivity. Heavy marijuana users (both deprived and nondeprived) displayed increased startle potentiation during threat of unpredictable electric shock relative to minimal use controls. In contrast, marijuana deprivation had no effect on startle potentiation. Startle potentiation was also increased among users who reported greater stress-coping motives for their marijuana use and users with cannabis use disorder diagnoses. To our knowledge, this is the 1st study to demonstrate increased reactivity to unpredictable stressors among heavy marijuana users. However, comparable increased unpredictable stressor reactivity among patients with alcohol and other substance use disorders has been previously documented. This relationship to heavy marijuana use is consistent with predictions from rodent addiction models regarding stress neuroadaptations following heavy, chronic drug use but could also represent an etiologically relevant premorbid risk characteristic. Finally, the clinical import of unpredictable stressor reactivity is reinforced by its relationships with stress-coping motives and cannabis use disorder status. (PsycINFO Database Record

Alcohol's effects on emotionally motivated attention, defensive reactivity and subjective anxiety during uncertain threats.

Developing a better understanding of how and under what circumstances alcohol affects the emotions, cognitions and neural functions that precede and contribute to dangerous behaviors during intoxication may help to reduce their occurrence. Alcohol intoxication has recently been shown to reduce defensive reactivity and anxiety more during uncertain vs certain threat. However, alcohol's effects on emotionally motivated attention to these threats are unknown. Alcohol may disrupt both affective response to and attentional processing of uncertain threats making intoxicated individuals less able to avoid dangerous and costly behaviors. To test this possibility, we examined the effects of a broad range of blood alcohol concentrations on 96 participants' sub-cortically mediated defensive reactivity (startle potentiation), retrospective subjective anxiety (self-report) and cortically assessed emotionally motivated attention (probe P3 event related potential) while they experienced visually cued uncertain and certain location electric shock threat. As predicted, alcohol decreased defensive reactivity and subjective anxiety more during uncertain vs certain threat. In a novel finding, alcohol dampened emotionally motivated attention during uncertain but not certain threat. This effect appeared independent of alcohol's effects on defensive reactivity and subjective anxiety. These results suggest that alcohol intoxication dampens processing of uncertain threats while leaving processing of certain threats intact.

Altered subjective reward valuation among female heavy marijuana users.

Maladaptive decision-making is a cardinal feature of drug use, contributing to ongoing use, and reflecting alterations in how drug users assess uncertain reward value. Accumulating evidence indicates the consequences of heavy marijuana use are worse for female versus male animals and humans, but research assessing sex differences in reward-related decision-making among marijuana users remains scarce. We examined sex differences in the subjective valuation of certain and uncertain rewards among heavy marijuana users (52; 26 male and 26 female) and controls (52; 26 male and 26 female). We offered male and female heavy marijuana users and controls monetary rewards of certain and uncertain (probabilistic) values. We measured how preferences for uncertain rewards varied by the objective value of those rewards, moderators of reward uncertainty, Marijuana Group and Sex. Men were more sensitive to changes in the objective value of uncertain rewards than women. However, this effect of Sex differed by Marijuana Group. Female heavy marijuana users were more sensitive to changes in uncertain reward value, particularly when the "stakes" were high (i.e., greater difference between potential uncertain rewards), than female controls. Female heavy marijuana users' sensitivity to changes in the value of high stakes uncertain rewards was comparable to male marijuana users and controls. In contrast, male marijuana users' sensitivity to changes in the value of high stakes uncertain rewards did not differ from male controls. These results suggest sex differences in sensitivity to high risk rewards may be one pathway contributing to severer consequences of heavy marijuana use among women. (PsycINFO Database Record

Altered subjective reward valuation among drug-deprived heavy marijuana users: Aversion to uncertainty.

Marijuana is the most commonly used illicit drug in the United States and its use is rising. Nonetheless, scientific efforts to clarify the risk for addiction and other harm associated with marijuana use have been lacking. Maladaptive decision-making is a cardinal feature of addiction that is likely to emerge in heavy users. In particular, distorted subjective reward valuation related to homeostatic or allostatic processes has been implicated for many drugs of abuse. Selective changes in responses to uncertainty have been observed in response to intoxication and deprivation from various drugs of abuse. To assess for these potential neuroadaptive changes in reward valuation associated with marijuana deprivation, we examined the subjective value of uncertain and certain rewards among deprived and nondeprived heavy marijuana users in a behavioral economics decision-making task. Deprived users displayed reduced valuation of uncertain rewards, particularly when these rewards were more objectively valuable. This uncertainty aversion increased with increasing quantity of marijuana use. These results suggest comparable decision-making vulnerability from marijuana use as other drugs of abuse, and highlights targets for intervention.

Empirically based comparisons of the reliability and validity of common quantification approaches for eyeblink startle potentiation in humans.

Startle potentiation is a well-validated translational measure of negative affect. Startle potentiation is widely used in clinical and affective science, and there are multiple approaches for its quantification. The three most commonly used approaches quantify startle potentiation as the increase in startle response from a neutral to threat condition based on (1) raw potentiation, (2) standardized potentiation, or (3) percent-change potentiation. These three quantification approaches may yield qualitatively different conclusions about effects of independent variables (IVs) on affect when within- or between-group differences exist for startle response in the neutral condition. Accordingly, we directly compared these quantification approaches in a shock-threat task using four IVs known to influence startle response in the no-threat condition: probe intensity, time (i.e., habituation), alcohol administration, and individual differences in general startle reactivity measured at baseline. We confirmed the expected effects of time, alcohol, and general startle reactivity on affect using self-reported fear/anxiety as a criterion. The percent-change approach displayed apparent artifact across all four IVs, which raises substantial concerns about its validity. Both raw and standardized potentiation approaches were stable across probe intensity and time, which supports their validity. However, only raw potentiation displayed effects that were consistent with a priori specifications and/or the self-report criterion for the effects of alcohol and general startle reactivity. Supplemental analyses of reliability and validity for each approach provided additional evidence in support of raw potentiation.

Happiness cools the warm glow of familiarity: psychophysiological evidence that mood modulates the familiarity-affect link.

People often prefer familiar stimuli, presumably because familiarity signals safety. This preference can occur with merely repeated old stimuli, but it is most robust with new but highly familiar prototypes of a known category (beauty-in-averageness effect). However, is familiarity always warm? Tuning accounts of mood hold that positive mood signals a safe environment, whereas negative mood signals an unsafe environment. Thus, the value of familiarity should depend on mood. We show that compared with a sad mood, a happy mood eliminates the preference for familiar stimuli, as shown in measures of self-reported liking and physiological measures of affect (electromyographic indicator of spontaneous smiling). The basic effect of exposure on preference and its modulation by mood were most robust for prototypes (category averages). All this occurs even though prototypes might be more familiar in a happy mood. We conclude that mood changes the hedonic implications of familiarity cues.

Dissociable effects of hippocampus lesions on expression of fear and trace fear conditioning memories in rats.

The role of the hippocampus in memory is commonly investigated by comparing fear conditioning paradigms that differ in their reliance on the hippocampus. For example, the dorsal (septal) portion of the hippocampus is involved in trace, but not delay fear conditioning, two Pavlovian paradigms in which only the relative timing of stimulus presentation is varied. However, a growing literature implicates the ventral (temporal) portion of the hippocampus in the expression of fear, irrespective of prior training. The current experiments evaluated the relative contributions of the dorsal and ventral portions of the hippocampus to trace fear conditioning specifically vs. the expression of conditioned fear in general. Lesions restricted to the dorsal hippocampus blocked acquisition of trace fear conditioning. Larger lesions, also including an adjacent portion of the ventral hippocampus, were required to impair retrieval of trace fear conditioning. Delay fear conditioning was not disrupted in either case. In contrast, lesions that encompassed almost the entire dorsal and ventral hippocampus disrupted expression of both trace and delay fear conditioning. The current data suggest distinct roles in fear conditioning for three regions of the hippocampus: the septal zone is required for acquisition of trace fear conditioning, a larger portion of the hippocampus is critical for memory retrieval, and a region including the temporal zone is required for expression of both trace and delay fear conditioning. These findings are consistent with evidence suggesting the neuroanatomical and functional segregation of the hippocampus into three zones along its septal-temporal axis.