Introduction Product characteristics that impact e-cigarette appeal by altering the sensory experience of vaping need to be identified to formulate evidence-based regulatory policies. While products that contain sweet flavorings and produce a “throat hit” (i.e., desirable airway irritation putatively caused by nicotine) are anecdotally cited as desirable reasons for vaping among young adults, experimental evidence of their impact on user appeal is lacking. This experiment applied a novel laboratory protocol to assess whether: (1) sweet flavorings and nicotine affect e-cigarette appeal; (2) sweet flavorings increase perceived sweetness; (3) nicotine increases throat hit; and (4) perceived sweetness and throat hit are associated with appeal. Methods Young adult vapers (N=20; age 19–34) self-administered 20 standardized doses of aerosolized e-cigarette solutions varied according to a 3 flavor (sweet [e.g., cotton candy] vs. non-sweet [e.g., tobacco-flavored] vs. flavorless) × 2 nicotine (6 mg/mL nicotine vs. 0 mg/mL [placebo]) double-blind, cross-over design. Participants rated appeal (liking, willingness to use again and perceived monetary value), perceived sweetness and throat hit strength after each administration. Results Sweet-flavored (vs. non-sweet and flavorless) solutions produced greater appeal and perceived sweetness ratings. Nicotine produced greater throat hit ratings than placebo, but did not significantly increase appeal nor interact with flavor effects on appeal. Controlling for flavor and nicotine, perceived sweetness was positively associated with appeal ratings; throat hit was not positively associated with appeal. Conclusions Further identification of compounds in e-cigarette solutions that enhance sensory perceptions of sweetness, appeal, and utilization of e-cigarettes are warranted to inform evidence-based regulatory policies.

The anterior cingulate cortex (ACC) is a component of the limbic system implicated in a wide variety of functions spanning motor and sensory information processing, memory, attention, novelty detection, and comparisons of expectation versus outcome. It remains unclear how much of this functional diversity stems from differences in methodology or interpretation versus truly reflecting the range of processes in which the ACC is involved. In the present study, ACC neuronal activity was examined in freely behaving mice (C57BL6/J) under conditions allowing investigation of many of the cited functions in conditions free from externally applied rules: tests of novel object and novel location recognition memory. Behavioral activity and neuronal activity were recorded first in the open field, during the initial exposure and subsequent familiarization to two identical objects, and finally during the recognition memory tests. No discernible stable firing correlates of ACC neurons were found in the open field, but the addition of objects led to lasting changes in the firing patterns of many ACC neurons around one or both of the object locations. During the novel location test, some neurons followed the familiar object to its new location, others fired exclusively where the object had been, and yet others fired to both current and former object locations. Many of these same features were observed during tests of object recognition memory. However, the magnitude of the neuronal preference for the novel or the familiar object was markedly greater than that observed during either the tests of location recognition or novel object preferences in animals that did not exhibit the expected behavior. The present study reveals, for the first time, single-neuron correlates of object and location recognition behaviors in the rodent ACC and suggests that neurons of the ACC provide a distributed representation of all of the salient features of a task.

Exercise training is widely used for neurorehabilitation of Parkinson’s disease (PD). However, little is known about the functional reorganization of the injured brain after long-term aerobic exercise. We examined the effects of 4 weeks of forced running wheel exercise in a rat model of dopaminergic deafferentation (bilateral, dorsal striatal 6-hydroxydopamine lesions). One week after training, cerebral perfusion was mapped during treadmill walking or at rest using [14C]-iodoantipyrine autoradiography. Regional cerebral blood flow-related tissue radioactivity (rCBF) was analyzed in three-dimensionally reconstructed brains by statistical parametric mapping. In non-exercised rats, lesions resulted in persistent motor deficits. Compared to sham-lesioned rats, lesioned rats showed altered functional brain activation during walking, including: 1. hypoactivation of the striatum and motor cortex; 2. hyperactivation of non-lesioned areas in the basal ganglia-thalamocortical circuit; 3. functional recruitment of the red nucleus, superior colliculus and somatosensory cortex; 4. hyperactivation of the ventrolateral thalamus, cerebellar vermis and deep nuclei, suggesting recruitment of the cerebellar-thalamocortical circuit; 5. hyperactivation of limbic areas (amygdala, hippocampus, ventral striatum, septum, raphe, insula). These findings show remarkable similarities to imaging findings reported in PD patients. Exercise progressively improved motor deficits in lesioned rats, while increasing activation in dorsal striatum and rostral secondary motor cortex, attenuating a hyperemia of the zona incerta and eliciting a functional reorganization of regions participating in the cerebellar-thalamocortical circuit. Both lesions and exercise increased activation in mesolimbic areas (amygdala, hippocampus, ventral striatum, laterodorsal tegmental n., ventral pallidum), as well as in related paralimbic regions (septum, raphe, insula). Exercise, but not lesioning, resulted in decreases in rCBF in the medial prefrontal cortex (cingulate, prelimbic, infralimbic). Our results in this PD rat model uniquely highlight the breadth of functional reorganizations in motor and limbic circuits following lesion and long-term, aerobic exercise, and provide a framework for understanding the neural substrates underlying exercise-based neurorehabilitation.

OBJECTIVES: Electronic cigarettes (e-cigarettes) are available in nontraditional flavors (eg, fruit and candy) that are banned in combustible cigarettes in the United States. Whether adolescent use of e-cigarettes in nontraditional flavors prospectively predicts continuation of vaping and progression to more frequent vaping is unknown. METHODS: High school students in Los Angeles, California, completed 5 semiannual surveys (2014-2017 [10th grade to 12th grade]). Among past-6-month e-cigarette users at survey waves 1 to 4 (N = 478), e-cigarette flavor (or flavors) used was coded into 2 mutually exclusive categories at each wave (use of $1 nontraditional flavors [fruit, candy, sweet or dessert, buttery, blends or combinations, and other] versus exclusive use of tobacco, menthol or mint, or flavorless). Flavor used during waves 1 to 4 was modeled as a timevarying, time-lagged regressor of vaping status and frequency outcomes 6 months later at waves 2 to 5. RESULTS: Across waves 1 to 4, there were 739 (93.8%) observations of nontraditional-flavor use and 49 (6.2%) observations of exclusive use of tobacco, mint or menthol, or flavorless e-cigarettes. Use of e-cigarettes in nontraditional flavors (versus only tobacco, mint or menthol, or flavorless) was positively associated with vaping continuation (64.3% vs 42.9%; adjusted odds ratio = 3.76 [95% confidence interval 1.20 to 10.31]) and past-30-day number of puffs per nicotine vaping episode (mean: 3.1 [SD 5.5] vs 1.5 [SD 3.8]; adjusted rate ratio = 2.41 [95% confidence interval 1.08 to 5.92]) 6 months later. Flavor used was not associated with the subsequent number of past-30-day vaping days or episodes per day. CONCLUSIONS: Adolescents who vaped e-cigarettes in nontraditional flavors, compared with those who exclusively vaped tobacco-flavored, mint-or menthol-flavored, or flavorless e-cigarettes, were more likely to continue vaping and take more puffs per vaping occasion 6 months later. WHAT'S KNOWN ON THIS SUBJECT: Electronic cigarettes (e-cigarettes) in nontraditional flavors (eg, fruit and candy) are commonly used at e-cigarette use initiation by youth. Whether exposure to e-cigarettes in nontraditional flavors after youth start vaping prospectively predicts persistence and progression of vaping is unknown. WHAT THIS STUDY ADDS: This study provides the first prospective longitudinal evidence indicating that among youth who vape e-cigarettes, use of e-cigarettes in nontraditional flavors is positively associated with subsequent persistence of vaping and puffs per vaping episode.

Heightened negative affect during acute tobacco abstinence in women relative to men could be an important factor underlying sex differences in smoking motivation. However, little controlled experimental work addresses this hypothesis. The current study investigated sex differences in withdrawal-related negative affect, time to start smoking on a lab analogue smoking lapse task, and the interrelation between sex, withdrawal-related negative affect, and smoking lapse behavior. Following a baseline session, current smokers (women: n = 68, men: n = 131) attended two counterbalanced lab sessions (16 hours smoking abstinence and ad libitum smoking) during which they completed self-report measures of mood and withdrawal symptoms followed by a laboratory analogue smoking lapse task. In this task participants are monetarily rewarded for delaying smoking. Performance on this task serves as an analogue model of smoking lapse behavior by measuring smoker’s capability to resist temptation to smoke under conditions where abstinence is advantageous. Females showed greater abstinence induced increases in composite negative affect as well as several particular negative affect states (i.e., POMS Anger, Anxiety, Depression, and Confusion, ps < .05) but no differences in abstinence induced changes in other forms of affect or craving. Females also exhibited marginally greater abstinence induced decreases in their willingness to delay smoking for money (p = .10), which was mediated by abstinence induced increases in anger (p < .05). These results suggest that differential sensitivity to abstinence induced negative affect, particularly anger, could underlie sex specific smoking patterns. Negative affect during tobacco abstinence may be an important factor for understanding and treating nicotine addiction in women.