IMPULSIVITY, mental health STATE and emotion regulation MODULATE alcohol and marijuana use in a sample of Argentinean citizens.

Impulsivity and substance-related outcomes share a complex relationship, as various facets of impulsivity exhibit distinct associations with different drug-related outcomes. This study examines the associations between frequency and quantity of alcohol and marijuana use, with impulsivity traits, psychological distress, and the utilization of emotion regulation strategies. A survey asked Argentinian citizens (n=1507, 356 men) about frequency and quantity of alcohol or marijuana use on each day of a typical week, as well as anxiety, stress and depression symptoms (DASS-21), impulsivity-like traits (UPPS-P) and emotion regulation strategies (ERQ). The two-month prevalence of alcohol or marijuana use was 80.1%, and 27.2%, respectively. Lower premeditation was significantly (p<.05) and negatively associated with both frequency and quantity of alcohol consumed, whereas negative and positive urgency were positively and significantly (p<.05) associated with quantity of alcohol or marijuana use, respectively. Greater depression symptoms predicted greater quantity of alcohol use; whereas lower emotional suppression or lower cognitive reappraisal were significantly (p<.05) associated with a greater frequency of alcohol or marihuana use. Sensation seeking was significantly (p<.05) and positively associated with frequency of marijuana use. Individuals with higher levels of impulsivity-like traits, higher levels of depression or lower use of emotional regulation abilities appeared to be at a higher risk of alcohol or marijuana use. In this sample, the use of alcohol (though not marijuana) seems to fit a negative reinforcement pathway. The study suggests that individuals with risk factors for drug misuse could benefit from interventions aimed at enhancing emotion regulation.

Neurobehavioral alterations induced by third-trimester gestation-equivalent ethanol exposure are inhibited by folate administration.

Prenatal ethanol exposure (PEE) causes several neurobehavioral impairments in the fetus. Postnatal days (PDs) 4-9 in rodents are considered equivalent to the third trimester of gestation in humans. This period is characterized by high rates of synaptogenesis and myelination and the maturation of key structures and transmitter systems. Nutritional supplements, such as folate, have gained attention as putative treatments to mitigate detrimental effects of PEE. Folate is crucial for DNA synthesis and amino acid metabolism and heightens antioxidant defenses. The present study examined neurobehavioral effects of the concurrent administration of folate (20 mg/kg/day) and ethanol (5 g/kg/day) during PDs 4-9 in male and female Wistar rats. During PDs 16-18, the rat pups were tested for anxiety-like and exploratory activity in the light-dark box (LDB), open field (OF), and concentric square field (CSF) tests. After weaning, they were tested for sucrose preference and ethanol intake. Neonatal ethanol exposure reduced body weight in infancy but did not enhance ethanol self-administration or significantly affect performance in the OF or LDB. Neonatal ethanol exposure also reduced sucrose intake in the preference test and increased shelter-seeking in the CSF, and folate significantly inhibited these effects. The present findings suggest that folate, a treatment that is devoid of serious side effects, can ameliorate some neurobehavioral effects of PEE.

Juvenile variable stress modulates, in female but not in male Wistar rats, ethanol intake in adulthood.

Early stress can increase vulnerability to psychopathological disorders, including substance use disorders. The effects of stress in the juvenile period of the rat, that extends between weaning and the onset of adolescence (equivalent to late human childhood), have received little attention. This study assessed short and long-term behavioral effects of juvenile stress, with a focus on effects on ethanol intake. Male and female Wistar rats were exposed to variable stress (restraint, elevated platform, forced swimming, and social instability) or to restraint stress only, between postnatal days 26 to 29 (PDs 26-29). During adolescence, patterns of anxiety (PD 31) and depression (PD 33), ethanol intake (PDs 36-45) and behavioral sensitivity to the effects of acute stress (PD 47) were evaluated. In adulthood, alcohol ingestion was assessed through two-bottle ethanol intake tests (PDs 75-85). An additional experiment measured blood ethanol levels after a limited access intake session in adolescence. Exposure to juvenile variable stress exerted very mild effects in adolescence, but reduced ethanol ingestion in adulthood, in females only. Ethanol intake during the limited access session was significantly correlated to blood alcohol levels. The results indicate that a schedule of juvenile variable stress that did not significantly alter anxiety-related behaviors induced, nonetheless, sexually dimorphic effects on ethanol intake in adulthood. Early stress exposure that reduced alcohol intake in Wistar rats has been associated with changes on brain opioid and dopamine receptors. These results highlight the impact of early stress exposure on adult female ethanol consumption and its possible underlying neurobiological changes, involving opioid and dopamine receptors.

Folate administration ameliorates neurobehavioral effects of prenatal ethanol exposure.

Background: Prenatal ethanol exposure (PEE) induces heightened ethanol intake at adolescence in preclinical studies. Ethanol intake alters the absorption of folate, a methyl-group donor critical for numerous cellular functions. The prenatal administration of folate is, therefore, a promising approach to reduce the effects of PEE.Objectives: Experiment 1 determined if prenatal folate modulated the effects of PEE on ethanol intake, anxiety-like response, and exploratory behaviors (Experiment 1) in Wistar rats. Experiment 2 assessed, in rats not given PEE, if postnatal folate reversed effects of ethanol exposure at postnatal days 28-42. Experiment 3 assessed if folate altered blood ethanol levels (BELs).Methods: Experiment 1 involved 242 (125 male) adolescent Wistar rats derived from dams given folate (20 mg/kg, gestational days - GD- 13-20) + ethanol (2.0 g/kg, GD 17-20), ethanol, or vehicle only at pregnancy. Experiment 2 involved 29 male adolescents administered vehicle or ethanol doses co-administered or not with folate. In Experiment 3 twelve adult females were tested for BELs after folate administration. These tests were applied: intake tests, light dark box (LDB), elevated plus maze, open field and concentric square field.Results: PEE heightened ethanol intake (η2 ps = 0.06-07) and induced hyperactivity and a reduced latency to exit the white area of the LDB (η2 ps = 0.12-17). These effects were partially inhibited by folate (p > .05). Rats exposed to ethanol exposure at adolescence exhibited reduced motor activity (η2 p = .17), regardless of folate treatment. Folate did not affect BELs.Conclusion: Folate administration should be considered as a preventive or acute treatment to attenuate the neurobehavioral effects of PEE.

Binge eating promotes ethanol self-administration in female rats with a history of intermittent ethanol exposure at adolescence.

BACKGROUND: Ethanol drinking begins during adolescence and, particularly when occurs in a binge-like pattern, exerts lingering adverse consequences. Pre-clinical studies indicate that intermittent ethanol exposure (IEA, a model of repeated ethanol intoxication), or binge eating (BE) can increase subsequent ethanol consumption. It is unknown if the promoting effects of BE upon ethanol drinking are found in female rats and are modulated by IEA at adolescence. This study assessed interactive effects between IEA and BE, upon ethanol drinking. METHODS: Female Wistar rats were given 4.0 g/kg ethanol, every other day from postnatal day 25-45. At adulthood, they were exposed to sessions in which a brief offering of a sizeable portion of highly palatable sugary pills was followed by a 120-min exposure to an ethanol bottle. RESULTS: Exploratory activity and recognition memory was not affected by the IEA. Glutathione peroxidase and catalase activity, and lipid peroxidation (measured in blood and brain at the end of the procedure) were not significantly affected by IEA or BE exposure. BE alone had a mild promoting effect on ethanol ingestion. Those rats that underwent IEA and BE, however, exhibited heightened and sustained ethanol self-administration (average of 2.12 g/kg/120 min, vs 1.15 g/kg/120 min of the other groups), that persisted throughout the BE sessions. IEA and a history of BE also promoted ethanol intake or preference in a two-bottle endpoint test. CONCLUSION: The study suggests that exposure to IEA exerts, when followed by BE at adulthood, promoting effects upon ethanol intake, particularly at concentrations ≥ 6%.

Factors Associated with Simultaneous or Concurrent Use of Alcohol and Marijuana in Argentina.

Background: The identification of factors promoting simultaneous alcohol and marijuana (SAM) use is important to promote early intervention efforts. The associations between impulsivity facets and SAM (or concurrent alcohol and marijuana, CAM) use have been analyzed in North American samples. These topics, however, remain unexplored in South American samples. This study assessed if internalizing symptoms, five impulsivity dimensions, and emotional regulation strategies differentiate between participants who reported last 2-month SAM use, CAM use, alcohol, or marijuana only use, or that reported no substance use. Methods: A sample of 1057 Argentinian citizens answered an online survey. A multinominal logistic regression was conducted on drug use membership. Results: Circa 25% of the sample reported SAM use. Higher sensation seeking differentiated between SAM use versus no substance use, and those with lower sensation seeking were more likely to be classified into the alcohol-only group or into the nonuse group, than into the SAM use group. Stress scores uniquely predicted membership into the alcohol-only category. Those with lower use of emotional suppression were more likely than nonusers to be classified in all drug use categories, except CAM use. Higher emotional suppression scores were associated with membership into the nonuse group or the alcohol-only group, when compared to the SAM use group. Hazardous drinking was significantly greater in SAM than in alcohol-only users. Conclusions: The study highlights the relevance of sensation seeking as a predictor of SAM use and pinpoints emotional suppression as common factor modulating hazardous drug use behaviors.

Administration of the sigma-1 receptor agonist PRE-084 at emerging adulthood, but not at early adolescence, attenuated ethanol-induced conditioned taste aversion in female rats.

Ethanol-induced conditioned taste aversion (CTA) is greater in late adolescence or young adulthood than in early adolescence. The role of the sigma receptor system in this age-related difference has not been extensively explored, particularly in female rats. This study assessed the effects of the activation of sigma-1 receptors (S1-R), via the selective S1-R agonist PRE-084, on ethanol-induced CTA at early or at terminal adolescence/emerging adulthood (28 or 56 days-old at the beginning of the procedures, respectively) in female Wistar rats. The modulation of binge-like ethanol intake by PRE-084 was assessed at terminal adolescence. S1-R activation at the acquisition of ethanol-induced CTA attenuated such learning at terminal but not at early adolescence. PRE-084 did not significantly affect ethanol binge drinking in the terminal adolescents. These results highlight the role of S1-R in ethanol-induced CTA and suggest that differential functionality of this transmitter system may underlie age-specific sensitivities to the aversive effects of ethanol.

Open field exposure facilitates the expression of a spatial, recognition memory.

Novelty seems to reduce the persistence of aversive memories and to modulate frustration responses, yet much less is known on how this treatment affects memories lacking hedonic or emotional content. The present study analyzed how a 5-min exposure to a novel open field modulated the expression of a spatial recognition memory. Experiment 1 indicated that male Wistar rats trained in a T-maze in which one goal arm is blocked exhibit, when tested 2 h later, preference for the novel arm. This recognition memory was impaired by the muscarinic cholinergic antagonist scopolamine. Postraining, but not pretraining, novelty exposure rescued the cognitive impairment induced by scopolamine (Experiment 2 and 3). Pretraining open field exposure alleviated the lack of memory expression, induced by imposing a 6 h delay between training and testing (Experiment 4). The study shows that a very brief exposure to novelty can improve expression of a spatial, recognition memory, a modulation that - in the case of the pretraining novelty exposure -- emerges even in spite of cholinergic blockade. The present results are consistent with research suggesting that novelty exposure can be an effective, non-pharmacological, treatment to modulate memory expression.

Sigma-1 antagonism inhibits binge ethanol drinking at adolescence.

BACKGROUND: Ethanol use during adolescence is a significant health problem, yet the pharmacological treatments to reduce adolescent binge drinking are scarce. The present study assessed, in male and female adolescent Wistar rats, if the sigma-1 receptor (S1-R) antagonists S1RA or BD-1063 disrupted ethanol drinking. METHODS: Three times a week, for two weeks, the rats received the S1-R antagonists. Thirty min later they were exposed, for 2 h, to a bottle of 8% or 10 % v/v ethanol. A 24 h, two-bottle, ethanol intake test was conducted after termination of these procedures. A subset of these rats was tested for recognition memory via the novel object recognition test. RESULTS: The rats given 64 mg/kg S1RA drank, in each binge session, significantly less than vehicle counterparts. Male rats given 4 or 16 mg/kg S1RA drank significantly less than those given 0 mg/kg in session 3 or in session 1 and 2, respectively; whereas female rats given 4 or 16 mg/kg drank significantly less than females given 0 mg/kg in session 2-5 or in sessions 2-6, respectively. Administration of 32 mg/kg, but not of 2 or 8 mg/kg, BD-1063 suppressed, across sessions, ethanol drinking. S1-R antagonism reduced absolute ethanol drinking at the two-bottle choice post-test. Recognition memory was not affected by the ethanol exposure. CONCLUSIONS: The results indicate that S1-R antagonists may be promising targets to prevent increases in ethanol intake at adolescence. The persistent effect of S1-R antagonism in free-choice drinking suggests that modulation of the S1-R is altering plastic effects associated with ethanol exposure.

Binge-Like, Naloxone-Sensitive, Voluntary Ethanol Intake at Adolescence Is Greater Than at Adulthood, but Does Not Exacerbate Subsequent Two-Bottle Choice Drinking.

The present study assessed the effects of ethanol exposure during adolescence or adulthood. We exposed Wistar rats, males or females, to self-administered 8-10% (v/v) ethanol (BINGE group) during the first 2 h of the dark cycle, three times a week (Monday, Wednesday, and Friday) during postnatal days (PDs) 32-54 or 72-94 (adolescent and adults, respectively). During this period, controls were only handled, and a third (IP) condition was given ethanol intraperitoneal administrations, three times a week (Monday, Wednesday, and Friday), at doses that matched those self-administered by the BINGE group. The rats were tested for ethanol intake and preference in a two-bottle (24 h long) choice test, shortly before (PD 30 or 70) and shortly after (PD 56 or 96) exposure to the binge or intraperitoneal protocol; and then tested for free-choice drinking during late adulthood (PDs 120-139) in intermittent two-bottle intake tests. Binge drinking was significantly greater in adolescents vs. adults, and was blocked by naloxone (5.0 mg/kg) administered immediately before the binge session. Mean blood ethanol levels (mg/dl) at termination of binge session 3 were 60.82 ± 22.39. Ethanol exposure at adolescence, but not at adulthood, significantly reduced exploration of an open field-like chamber and significantly increased shelter-seeking behavior in the multivariate concentric square field. The rats that had been initially exposed to ethanol at adolescence drank, during the intake tests conducted at adulthood, significantly more than those that had their first experience with ethanol at adulthood, an effect that was similar among BINGE, IP and control groups. The study indicates that binge ethanol drinking is greater in adolescent that in adults and is associated with heightened ethanol intake at adulthood. Preventing alcohol access to adolescents should reduce the likelihood of problematic alcohol use or alcohol-related consequences.