Cues associated with a single ethanol exposure elicit conditioned corticosterone responses in adolescent male but not female Sprague-Dawley rats.

It has been shown that ethanol-induced interleukin-6 (IL-6) in adult male Sprague-Dawley rats was sensitized by environmental stimuli paired with ethanol and was accompanied by a conditioned increase in corticosterone (CORT). Adolescent males showed ethanol-induced IL-6 conditioning more readily than adults. The present studies examined whether female adolescents display IL-6 conditioning and whether adolescents of either sex show CORT conditioning. Male and female (N = 212, n = 6-10) adolescent (postnatal day 33-40) rats were given ethanol (2 g/kg intraperitoneal injection; the unconditioned stimulus), either paired with a lavender-scented novel context (the conditioned stimulus) or explicitly unpaired from context. Rats were tested in the context without ethanol and brains/blood were collected. Adolescent females did not show signs of neuroimmune (Experiment 1) or CORT conditioning (Experiments 2-4). Paired males showed enhanced CORT to the scented context relative to unpaired counterparts when the interoceptive cue of a saline injection was used on test day (Experiment 2). Experiment 5 used a delayed conditioning procedure and showed that male paired adolescents showed significantly higher CORT in response to context, showing that classically conditioned CORT response was precipitated by environmental cues alone. These findings indicate that adolescent males may be predisposed to form conditioned associations between alcohol and environmental cues, contributing to adolescent vulnerability to long-lasting ethanol effects.

The Association Between Mindfulness Facets and Substance Use via Emotional Psychopathology and Coping Motives in Argentinian College Students.

Background: Prior studies suggest that lower levels of mindfulness contribute to the motivation of using alcohol to cope with distress. Research examining this possibility is scarce or limited to alcohol, but not marijuana, related outcomes. Objectives: We examined separate models (for alcohol and for marijuana) to determine the associations between trait mindfulness (describing, acting with awareness, non-judging, non-reactivity) and alcohol and marijuana outcomes (use indicators and negative consequences) via emotional psychopathology (i.e., a latent variable assessing symptoms of depression and anxiety) and alcohol/marijuana coping motives. Results: The final analytic sample consisted of 456 participants (Mean age = 22.96 ± 3.12 years; 66.2% women) for the alcohol model; and 232 participants (Mean age = 22.96 ± 3.01 years; 66.2% women) for the marijuana model. Two path models were conducted, such that indirect paths were examined for each trait mindfulness facet on alcohol/marijuana outcomes (e.g., describing → emotional psychopathology → alcohol coping motives → binge drinking frequency). Within the comprehensive alcohol model, describing, acting with awareness, non-judging and non-reactivity were associated with less binge drinking frequency and lower number of alcohol-related negative consequences via lower severity of emotional psychopathology symptoms and lower endorsement of drinking to cope motives. For the marijuana model, describing, acting with awareness, and non-judging of inner experience were associated with less marijuana quantity (grams) consumed and lower number of marijuana-related negative consequences via lower severity of emotional psychopathology symptoms and lower endorsement of marijuana coping motives. Conclusions: Prevention and intervention programs of alcohol and marijuana in Argentina may benefit from improving mindfulness skills and targeting emotional psychopathology and motives to use drugs, to prevent or reduce negative drug-related consequences.

Utility of the Brief Young Adult Alcohol Consequences Questionnaire to Identify College Students At-Risk for Alcohol Related Problems: Relative Operating Characteristics across Seven Countries.

Background: It is important to identify students who would benefit from early interventions to reduce harmful drinking patterns and associated consequences. the Brief Young Adult Alcohol Consequences Questionnaire (B-YAACQ) could be particularly useful as a screening tool in university settings. Objectives. The present study examined the utility of the B-YAACQ to distinguish among students at-risk for problematic alcohol use as measured by the AUDIT. Objectives: The present study examined the utility of the B-YAACQ to distinguish among students at-risk for problematic alcohol use as measured by the AUDIT. Methods: A sample of 6382 students (mean age=20.28, SD=3.75, 72.2% females) from seven countries (i.e., U.S., Canada, South-Africa, Spain, Argentina, Uruguay, England) completed the B-YAACQ, the AUDIT and different measures of alcohol use. Results: ROC analyses suggested that a cutoff score of 5 maximized the YAACQ's discrimination utility to differentiate between students at low versus moderate/high risk in the total sample and across countries (except in Canada, where the cutoff was 4). In addition, a cutoff of 7 differentiated between students at low/moderate versus high risk in the total sample, while cutoffs of 10, 9, 8 and 7 differentiate between students at low/moderate versus high risk in Uruguay, U.S and Spain (10), Argentina (9), England (8), and Canada and South-Africa (7), respectively. Students classified at the three risk levels (i.e., low, moderate and high) differed in age (i.e., a younger age was associated with higher risk) and drinking patters (i.e., higher drinking frequency, quantity, binge drinking and AUDIT and B-YAACQ scores in the higher risk groups). Conclusions: This study suggest that the B-YAACQ is a useful tool to identify college students at-risk for experiencing problematic patterns of alcohol use.

Interoception Primes Emotional Processing: Multimodal Evidence from Neurodegeneration.

Recent frameworks in cognitive neuroscience and behavioral neurology underscore interoceptive priors as core modulators of negative emotions. However, the field lacks experimental designs manipulating the priming of emotions via interoception and exploring their multimodal signatures in neurodegenerative models. Here, we designed a novel task that involves interoceptive and control-exteroceptive priming conditions followed by post-interoception and post-exteroception facial emotion recognition (FER). We recruited 114 participants, including healthy controls (HCs) as well as patients with behavioral variant frontotemporal dementia (bvFTD), Parkinson's disease (PD), and Alzheimer's disease (AD). We measured online EEG modulations of the heart-evoked potential (HEP), and associations with both brain structural and resting-state functional connectivity patterns. Behaviorally, post-interoception negative FER was enhanced in HCs but selectively disrupted in bvFTD and PD, with AD presenting generalized disruptions across emotion types. Only bvFTD presented impaired interoceptive accuracy. Increased HEP modulations during post-interoception negative FER was observed in HCs and AD, but not in bvFTD or PD patients. Across all groups, post-interoception negative FER correlated with the volume of the insula and the ACC. Also, negative FER was associated with functional connectivity along the (a) salience network in the post-interoception condition, and along the (b) executive network in the post-exteroception condition. These patterns were selectively disrupted in bvFTD (a) and PD (b), respectively. Our approach underscores the multidimensional impact of interoception on emotion, while revealing a specific pathophysiological marker of bvFTD. These findings inform a promising theoretical and clinical agenda in the fields of nteroception, emotion, allostasis, and neurodegeneration.SIGNIFICANCE STATEMENT We examined whether and how emotions are primed by interoceptive states combining multimodal measures in healthy controls and neurodegenerative models. In controls, negative emotion recognition and ongoing HEP modulations were increased after interoception. These patterns were selectively disrupted in patients with atrophy across key interoceptive-emotional regions (e.g., the insula and the cingulate in frontotemporal dementia, frontostriatal networks in Parkinson's disease), whereas persons with Alzheimer's disease presented generalized emotional processing abnormalities with preserved interoceptive mechanisms. The integration of both domains was associated with the volume and connectivity (salience network) of canonical interoceptive-emotional hubs, critically involving the insula and the anterior cingulate. Our study reveals multimodal markers of interoceptive-emotional priming, laying the groundwork for new agendas in cognitive neuroscience and behavioral neurology.

The functional and molecular effects of problematic alcohol consumption on skeletal muscle: a focus on athletic performance.

Background: Chronic alcohol misuse is associated with alcoholic myopathy, characterized by skeletal muscle weakness and atrophy. Moreover, there is evidence that sports-related people seem to exhibit a greater prevalence of problematic alcohol consumption, especially binge drinking (BD), which might not cause alcoholic myopathy but can negatively impact muscle function and amateur and professional athletic performance.Objective: To review the literature concerning the effects of alcohol consumption on skeletal muscle function and structure that can affect muscle performance.Methodology: We examined the currently available literature (PubMed, Google Scholars) to develop a narrative review summarizing the knowledge about the effects of alcohol on skeletal muscle function and exercise performance, obtained from studies in human beings and animal models for problematic alcohol consumption.Results: Exercise- and sport-based studies indicate that alcohol consumption can negatively affect muscle recovery after vigorous exercise, especially in men, while women seem less affected. Clinical studies and pre-clinical laboratory research have led to the knowledge of some of the mechanisms involved in alcohol-related muscle dysfunction, including an imbalance between anabolic and catabolic pathways, reduced regeneration, increased inflammation and fibrosis, and deficiencies in energetic balance and mitochondrial function. These pathological features can appear not only under chronic alcohol misuse but also in other alcohol consumption patterns.Conclusions: Most laboratory-based studies use chronic or acute alcohol exposure, while episodic BD, the most common drinking pattern in amateur and professional athletes, is underrepresented. Nevertheless, alcohol consumption negatively affects skeletal muscle health through different mechanisms, which collectively might contribute to reduced sports performance.

Sensitive period for the acceptance of unpalatable flavors in the presence of a preexposed odor in infant rats.

It has been shown that exposure to familiar odors facilitate the acceptance of bitter flavors in preweanling rats, yet it unknown how long this phenomenon persists. This study assessed, in 9- or 15-day-old Wistar rats, the influence of a familiar scent (i.e., lemon) on the intake of and behavioral responsiveness (i.e., mouthing, paw lick, chin rub, head shake, among other taste reactivity responses) elicited by a 0.1% quinine solution. The results showed heightened quinine intake in 9-day-old rats that had been preexposed to the odor, when compared to non-preexposed controls. This result was replicated in Experiment 2, which also documented no alterations in behavioral responsiveness toward quinine in the 9-day-old rats, as a function of the pre-exposure. More importantly, 15-day-old rats exhibited no alterations in intake or behavioral responsiveness toward quinine as a function of odor pre-exposure. These results suggest that the effects of odor pre-exposure upon acceptance of bitter tastes may occur within a sensitive period for the acceptance of bitter food.

Pre- and postnatal alcohol exposure delays, in female but not in male rats, the extinction of an auditory fear conditioned memory and increases alcohol consumption.

Repeated exposure to alcohol increases retrieval of fear-conditioned memories, which facilitates, among other factors, the emergence of post-traumatic stress disorder (PTSD). Individuals with PTSD are more likely to develop alcohol and substance abuse related disorders. We assessed if prenatal and early postnatal alcohol exposure (PAE) increased the susceptibility to retain aversive memories and if this was associated with subsequent heightened alcohol consumption. Pregnant Sprague-Dawley rats were exposed for 22 hr/day, throughout pregnancy and until postnatal Day 7 to a single bottle of sucralose - sweetened 10% alcohol solution (PAE Group), or to a single bottle of tap water and sucralose (Control Group). Auditory fear conditioning (AFC) was performed in the adolescent offspring at postnatal Day 40. Freezing was measured during acquisition, retention and extinction phases, followed by 3 weeks of free choice alcohol intake. Female, but not male, PAE rats exhibited impaired extinction of the aversive memory, a finding associated with higher levels of 3-4 Dihidroxyphenylacetic acid (DOPAC) in the nucleus accumbens and heightened alcohol intake, respect to controls. These findings suggest that PAE makes females more vulnerable to long-term retention of aversive memories, which coexist with heightened alcohol intake. These findings are reminiscent of those of PTSD.

Exposure to maternal odor enhances intake of a taste that mimicks the sensory attributes of ethanol.

Early exposure to ethanol increases subsequent acceptance of this drug. Little attention, however, has been devoted to the interaction of the taste of the drug with other, familiar or non-familiar, odors contingent with ethanol access, particularly early in ontogeny. This study assessed the influence of exposure to maternal odor on intake and grasp responses to an artificial nipple providing a solution (a sucrose-quinine mix) that emulates the taste of alcohol, in 4-day-old rat pups. The results showed that the mother's odor enhanced intake from and seeking responses to an artificial nipple that provided the solution that mimicked the taste of alcohol (Experiment 1). This pattern of results was not evoked by the odor of an unrelated dam (Experiment 2), nor was it observed when the nipple delivered water. The main new finding of the present study is that 4-day-old rats tested in the presence of the mother (and hence exposed to her odor cues) exhibited enhanced seeking and intake of a solution that mimics the chemosensory properties of ethanol.

Consummatory succesive positive contrast produced by the downshift of an aversive solution in infant rats.

Subjects trained in successive positive contrast are usually given an appetitive stimulus of relatively low quality during a pre-shift, followed by exposure to a significantly greater quality of the same stimulus. Enhanced responsiveness to the high-quality stimulus during the post-shift phase, compared to a control group that receives the superior reward in both phases, is taken as an index of successive positive contrast. Successive positive contrast reports are rare, probably due to performance limitations inherent to the experimental protocols available. We exposed infant rats (14 days old at the start of training) to .1% or .01% quinine during 4, 10 min, trials (pre-shift phase). All animals were then given two trials of exposure to .01% quinine (post-shift phase). During the pre-shift the level of intake was greater in pups stimulated with the relatively less aversive .01% quinine solution. These animals also exhibited, compared to those stimulated with .1% quinine, lower emission of the aversive response paw treading. During the post-shift phase, the group that had been exposed to .1% quinine exhibited significantly greater intake of .01% quinine, along with a reduction in the emission of paw treading and an enhancement in paw licking, an ingestive, appetitive response. Altogether, the evidence is suggestive of the emergence of consummatory successive positive contrast during the second week of life of the rat. To our knowledge, this is the first evidence of positive contrast using an aversive solution.

Effects of ethanol exposure in a familiar or isolated context during infancy on ethanol intake during adolescence.

Early exposure to ethanol affects ethanol intake later in life. This early experience encompasses exposure to social stimuli and the pharmacological and orosensory properties of ethanol. The specific contribution of each type of stimulus to subsequent ethanol intake remains unknown. We assessed the intake of various concentrations of ethanol in a familiar or isolated context during infancy and the lingering effects of this experience on ethanol intake during adolescence. On postnatal day 3 (PD3), PD7, and PD11, rats were given 5% ethanol or water in a nursing or isolated context (Experiments 1 and 2). Intake tests (ethanol vs. water) were conducted during adolescence. Experiment 2 matched the amount of fluid ingested during infancy in both contexts and subsequently tested ethanol consumption during adolescence. The results revealed a facilitative effect of the nursing context on fluid intake during the tests in infancy. Pups stimulated with ethanol but not water in the isolated context exhibited an increase in ethanol consumption during adolescence. This effect disappeared when the isolated infants were matched to receive the same amount of ethanol ingested by their nursed counterparts. In Experiment 3, isolated infant rats were exposed to different ethanol concentrations (.0%, 2.5%, 5.0%, and 10.0%), and drug consumption was tested during adolescence. This exposure increased adolescent ethanol intake, regardless of the alcohol concentration (Experiment 3). The common denominators that resulted in enhanced ethanol intake during adolescence were preexposure to ethanol via active consumption of the drug that induced a low-to-moderate level of intoxication in an isolated context.

Brief prenatal ethanol exposure alters behavioral sensitivity to the kappa opioid receptor agonist (U62,066E) and antagonist (Nor-BNI) and reduces kappa opioid receptor expression.

BACKGROUND: Approximately 10 to 15% of women consume alcohol (ethanol [EtOH]) during pregnancy in the United States. Even low amounts of EtOH consumption during pregnancy can elicit long-term consequences. Prenatal experience with as few as 3 drinks has been associated with increase problem drinking in adulthood. Such effects are corroborated in rodents; however, the underlying neural adaptations contributing to this effect are not clear. In the current set of experiments, we investigated whether changes in EtOH responding following prenatal EtOH exposure involved kappa opioid receptor activation and expression. METHODS: Sprague-Dawley rats were prenatally exposed to low levels of alcohol (1.0 g/kg) during late gestation (gestational days 17 to 20 [GD17-20]) via intragastric intubation of pregnant dams. Following birth, EtOH intake, kappa- and mu-opioid-induced place conditioning, and kappa opioid receptor expression in mesolimbic brain regions were assessed in infant rats (postnatal days 14 to 15 [PD14-15]) that were offspring of dams given EtOH, vehicle, or untreated, during pregnancy. RESULTS: Animals exposed to prenatal alcohol drank more alcohol later in life and exhibited significant changes in the kappa opioid system. While control subjects found kappa opioid activation aversive, animals exposed to EtOH prenatally exhibited either no aversion or appetitive responding. Further analysis revealed that synaptosomal kappa opioid receptor expression was significantly decreased in brain areas implicated in responding to EtOH. CONCLUSIONS: Overall, these data suggest that prenatal EtOH affects kappa opioid function and expression and that these changes may be involved in increased drinking later in life.

Ontogeny of consummatory successive negative contrast in rats.

Consummatory successive negative contrast (cSNC) occurs when organisms repeatedly exposed to a high-magnitude reward are suddenly given a low-magnitude reward. This results in a significant reduction in the consumption of the devalued reinforcer, at a level even below that of a group which had been always exposed to the low-magnitude reinforcer. A scarcity of animal studies assessed the expression of this phenomenon during early development. Three experiments assessed age of cSNC onset in preweanling rats. Percent body weight gained (%BWG) and taste reactions associated with reinforcement devaluation were measured. A reduction in %BWG and a significant increase in emission of aversive hedonic behaviors, indicative of cSNC, occurred on postnatal day 18 (PD 18; Experiments 1 and 2), but not on PD 14 or PD 17 (Experiments 3a and 3b). The neurobiological mechanisms underlying these effects and theoretical implications are discussed.

Positive and Negative Pathways Linking Depressive Symptoms to Problematic Alcohol Use Among Argentinian College Students: An Examination of Positive and Negative Urgency Traits and Internal Drinking Motives.

Growing evidence suggests the tendency to act rashly under positive and negative emotions and affect-related drinking motives connect symptoms of mood disorders with alcohol-related problems. However, studies examining this sequence are scarce in Latin-American samples. The present study evaluated, in Argentinian college students (n = 403; 68.2% women; Mage = 21.03 ± 4.90), a sequential model of symptoms of depression, urgency traits, internal drinking motives, and problematic alcohol use. Path analysis was conducted to examine the direct and indirect associations between symptoms of depression and problematic alcohol use (heavy episodic drinking and alcohol-related negative consequences) via positive and negative urgency traits and internal drinking motives. Findings revealed indirect associations from depressive symptoms to problematic alcohol use via urgency traits and drinking motives (e.g. depression symptoms→positive [negative] urgency→enhancement [coping]→drinking problems). This suggests that students who experience more symptoms of depression may be more likely to react to these experiences of negative affect by engaging in heavy drinking episodes and encounter more alcohol-related problems. This seems to stem from a higher propensity to act rashly during intense emotional experiences and a greater motivation to drink as a means of regulating their mood. Future interventions aimed at preventing or reducing problematic alcohol use (especially among Argentinian young adults) might consider targeting these specific impulsivity traits as well as affect-related drinking motivations.

Ethanol-induced locomotor activity in adolescent rats and the relationship with ethanol-induced conditioned place preference and conditioned taste aversion.

Adolescent rats exhibit ethanol-induced locomotor activity (LMA), which is considered an index of ethanol's motivational properties likely to predict ethanol self-administration, but few studies have reported or correlated ethanol-induced LMA with conditioned place preference (CPP) by ethanol at this age. The present study assessed age-related differences in ethanol's motor stimulating effects and analyzed the association between ethanol-induced LMA and conventional measures of ethanol-induced reinforcement. Experiment 1 compared ethanol-induced LMA in adolescent and adult rats. Subsequent experiments analyzed ethanol-induced CPP and conditioned taste aversion (CTA) in adolescent rats evaluated for ethanol-induced LMA. Adolescent rats exhibit a robust LMA after high-dose ethanol. Ethanol-induced LMA was fairly similar across adolescents and adults. As expected, adolescents were sensitive to ethanol's aversive reinforcement, but they also exhibited CPP. These measures of ethanol reinforcement, however, were not related to ethanol-induced LMA. Spontaneous LMA in an open field was, however, negatively associated with ethanol-induced CTA.

Change in Psychoactive Substance Consumption in Relation to Psychological Distress During the COVID-19 Pandemic in Uruguay.

Objectives: This study aimed to analyse how the health crisis associated with the COVID-19 pandemic affected psychoactive substance consumption in Uruguay. Methods: An online survey was answered by 1,916 Uruguayan citizens between March and April 2020 regarding psychoactive substance use before and after the instauration of a recommended quarantine, increases in frequency and volume of use (during the quarantine) of the psychoactive substance they reported as having consumed the most in the year prior to the quarantine and psychological distress experienced during the last month. Results: The main substances consumed during the quarantine were alcohol, tobacco, marijuana and psychopharmaceuticals. Approximately 28% of respondents increased the volume (and 17.7%, the frequency) of use of the substance they had consumed the most the year before the instauration of the quarantine. Moreover, 5.7% initiated the consumption of a new psychoactive substance during the quarantine, mostly marijuana and psychopharmaceuticals. Psychological distress was significantly higher among women, participants under 30 and among those that increased the volume of their most or second preferred psychoactive substance. The group reporting an increase in the volume of use exhibited greater psychological distress. Conclusion: These results indicate an association between the instauration of the recommended quarantine in Uruguay and greater psychoactive substance use during the period as well as an association between increased psychoactive substance use during this period and levels of psychological stress. These results are relevant in terms of public health and policies.

Genetic and environmental influences on ethanol consumption: perspectives from preclinical research.

BACKGROUND: Alcohol use disorders (abuse and dependence, AUD) are multifactorial phenomena, depending on the interplay of environmental and genetic variables. METHOD: This review describes current developments in animal research that may help (a) develop gene therapies for the treatment of alcoholism, (b) understand the permissive role of stress on ethanol intake, and (c) elucidate why exposure to ethanol early in life is associated with a greater risk of AUD. RESULTS: The polymorphisms found in liver alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) affect the elimination of ethanol and the susceptibility to ethanol intake. A highly active ADH protects against alcoholism, an effect related to a presteady state burst in arterial acetaldehyde. Social stressors, such as repeated early maternal separation or social defeat, exert a permissive effect on ethanol intake, perhaps by altering the normal development of the hypothalamic-pituitary-adrenal axis. Ethanol exposure during gestation, infancy, or adolescence increases the likelihood of AUD later in life. Early perception of ethanol's positive and negative (anti-anxiety) reinforcing effects may play a role in this phenomenon. CONCLUSIONS: The review underscores the advantages of using preclinical animal models of AUD and highlights points of intersection between the topics to help design a more integrated approach for the study of alcohol-related problems.

Offspring of male rats exposed to binge alcohol exhibit heightened ethanol intake at infancy and alterations in T-maze performance.

Alcohol use is associated with a variety of negative consequences, including heightened likelihood of cognitive impairment, proclivity to alcohol use disorders (AUD), and alterations in the drinker's offspring. Children and rodents exposed to alcohol during pregnancy, or those whose fathers consumed alcohol prior to mating, often exhibit neurodevelopmental, physiological, and behavioral deficits. The present study assessed cognitive function and alcohol intake in male and female rats that were offspring of alcohol-exposed fathers. Adult male rats were exposed to alcohol or vehicle (0.0 or 2.0 g/kg, respectively; twice daily for 2 days followed by a rest day, for a total of eight alcohol or vehicle exposure days), or were left untreated and then mated with non-manipulated females. The offspring were assessed for alcohol intake, via intraoral infusion, followed by cognitive assessment via an alternating T-maze task. The results indicated that paternal ethanol exposure, prior to breeding, resulted in offspring that consumed significantly more ethanol than vehicle or untreated controls. Furthermore, the offspring of alcohol-exposed fathers exhibited a significant failure to initiate and complete the T-maze performance tests. Although, when they did engage in the tests they performed at the level of controls (i.e., 80% correct). The present results add to a growing body of literature suggesting that paternal pre-conception alcohol exposure can have deleterious effects on the offspring.

Conditioning the neuroimmune response to ethanol using taste and environmental cues in adolescent and adult rats.

IMPACT STATEMENT: A combined odor and taste cue was paired with a binge-like ethanol exposure (4 g/kg intraperitoneal) using a single-trial learning paradigm. Re-exposure to the CS alone was sufficient to evoke a conditioned Interleukin (IL)-6 elevation in the amygdala in adolescents, an effect that was not observed in young adults. This demonstrates a particular sensitivity of adolescents to alcohol-associated cues and neuroimmune learning, whereas prior work indicated that adults require multiple pairings of ethanol to the CS in order to achieve a conditioned amygdala IL-6 response. While the role of immune conditioning has been studied in other drugs of abuse, these findings highlight a previously unknown aspect of alcohol-related learning. Given the emergent importance of the neuroimmune system in alcohol abuse, these findings may be important for understanding cue-induced reinstatement of alcohol intake among problem drinkers.

Motivational effects of intraorally-infused ethanol in rat pups in an operant self-administration task.

Motivational effects of self-administered ethanol have rarely been studied in preweanling rats due primarily to the lack of age-appropriate operant tasks. The present experiments assessed the hedonic effects of intraoral ethanol in infant rats self-administered by activating a touch sensor. On postnatal day (PD) 13 pups were pre-exposed to the drug's pharmacological and/or sensory effects. Operant sessions were conducted during PDs 14-16 (Experiments 1 and 2). Paired animals were placed in chambers equipped with a touch-sensitive disk and received an intraoral infusion of ethanol (3 or 5% v/v, 5 microl) after each sensor contact. Yoked controls were equated for number and distribution of ethanol infusions but had no control over the contingency between operant behavior and intraoral infusion. In Experiment 2, training trials were preceded by a non-reinforced phase. Paired pups performed fewer operant responses than controls and decreased their operant responses across sessions. These results suggest that intraoral self-administered ethanol has an aversive hedonic value in two-week old rats. Operant behavior seems to have been associated with aversive orosensory effects derived from intraoral ethanol infusion.

Maternal Odor Exposure Modulates Acceptance of a Bitter Taste in Newborn and Infant Rats.

The acceptance of bitter, aversive, substances during early life is enhanced by stimulation with familiar, pre-exposed odors. Newborn rats exhibited heightened grasp responses toward an artificial nipple dispensing quinine, and drank more of this bitter solution, if concurrently stimulated with a lemon odor they had been exposed to shortly after birth. It yet unknown, however, if odors made familiar via normative developmental milestones also acquire modulatory influence upon seeking and intake of basic tastants. The current study assessed the influence of exposure to maternal odor on intake and grasp responses toward a surrogate nipple providing quinine, in 3-day (Experiment 1) or 12-day (Experiment 2) old, Wistar rat pups. The results revealed enhanced seeking and intake of the bitter solution, but not of water, in animals tested in the presence of the mother (and hence exposed to its odor cues), at both ages, compared to counterparts given either no explicit odor stimulation or stimulation to the odor of an unrelated dam. These results, obtained with a biologically relevant odor, are consistent with those previously found with a neutral, arbitrary odor. It seems that during the early stages of development, familiar odors regulate the acceptance of non-palatable, otherwise rejected, flavors.