Tremblay et al. reported that chronic alcohol consumption did not result in a reduction in lipid intake and that a dietary regimen that provided a large fraction of energy in the form of alcohol increased the risk for a positive energy balance in a free-living state. It appears that alcohol may have a fat-sparing effect similar to that of carbohydrates and may cause fat gain. Suter et al. suggested that alcohol could result in excess body fat gain especially in the upper body. There is some evidence to suggest that obese individuals may be more susceptible to weight gain and the hyperlipidemic effects of alcohol consumption as compared to lean individuals. This is in contrast to epidemiological studies that report a negative association between alcohol consumption and adiposity. This may be explained by the induction of unregulated futile metabolic cycles that appear to significantly aid in the disposal of excess calories. In general, it appears that the effects of alcohol on body weight are controversial and it is likely that moderate consumption of alcohol that replaces calories from carbohydrates and fat is unlikely to result in weight gain.Alcohol has direct and demonstrable effects on athletic performance which may be due to its cardiovascular effects. McNaughton et al. demonstrated significant ergolytic effects in short and middle distance runners. The adverse effects were most prominent in events that were more dependent upon aerobic capacity . However there were no adverse effects observed in the 100 m run. Similarly, Kendrick et al.demonstrated a significant impairment in 60-minute treadmill time trial performance in trained athletes following alcohol ingestion. Heart rate and VO2 were significantly elevated in subjects after alcohol ingestion and only 1 out of 4 subjects could complete the run. This may be due, in part, to the significant hypoglycemia that the subjects experienced at the 60 minute time point. Acute alcohol consumption may also result in small but significant reductions in sustained power output.
Lecoultre et al. demonstrated thatacute ethanol ingestion resulted in a ~4% reduction in average cycling power output during a 60 minute timetrial. However,garden racks for sale the detrimental effect of alcohol on aerobic performance seems to be dose dependent with a threshold of 20 mmol/L, upon which the effect becomes significant. Consumption of alcohol 24 hours prior to exercise has also been shown to reduce aerobic performance by 11%. Some studies have failed to show reductions in exercise performance following alcohol consumption. However, this may be due to limitations in their experimental design as well as type of exercise used. For instance, the lack of ergolytic effects on exercise performance during bicycle ergometer testing may be due to the fact that using a stationary bicycle ergometer does not place significant motor coordination demands as compared to running. Alcohol can also impair recovery following exercise. It has been shown that alcohol can impair glycogen resynthesis after prolonged cycling. More importantly, alcohol seems to interfere with protein synthesis, most likely by suppressing the mTOR pathway, which is critical to facilitate repair and hypertrophy following strength training. Although alcohol seems to have an overall ergolytic effect on exercise performance, a well-known athlete reportedly consumed alcohol before a ski downhill competition. This is potentially a dangerous precedent especially since alcohol has significant effects on executive functions such as judgment and decision making while also having significant adverse effects on motor control and coordination. This has to be considered in sports requiring a high level of boldness and may have implications for pre-participation testing. In addition, the effects of an alcohol-induced hangover are poorly quantified and as such are relatively unknown and subject to further investigation in humans.Cannabis is one of the most frequently used psychoactive substances in the world and is the subject of major debates between proponents of the gateway hypothesis and advocates of legalization.
Proponents of the gateway hypothesis have argued that epidemiological studies indicate that the early use of cannabis is an important risk factor for initiating cocaine use, that cannabis dependence predicts cocaine dependence, that cannabis use may be associated with poor cognitive and psychiatric outcomes in adulthood, and that major changes in legalization of the possession, sale, and cultivation of cannabis in the United States may exacerbate these poor outcomes by increasing the level of cannabis use in adolescents and young adults.Currently, its use exceeds that of tobacco smoking among adolescents in the United States, in which 37.1% of high school seniors in 2017 reported using cannabis within the past year. Advocates of legalization and medicinal use argue that it is unclear whether the relationship between prior cannabis use and later cocaine use or cocaine use disorder is caused by cannabis use per se or other drug-associated factors, such as concomitant psychiatric disorders and socioeconomic status. However, epidemiological studies cannot establish causal relationships between the pharmacological effects of exposure to cannabis and the development of cocaine use. Preclinical studies provide a controlled way to study causal relationships between early-life cannabinoid exposure and cocaine use, including compulsive-like use, later in life. Previous studies reported that exposure to the cannabinoid receptor agonist WIN55,212-2 during adolescence decreased the reactivity of dopaminergic neurons to WIN , produced cross-tolerance to cocaine in adolescence, and produced cross-sensitization to the psychomotor effects of cocaine in adolescence but not in adulthood. This effect appears to be mediated by the modulation of eukaryotic initiation factors in the brain. Such modifications of key neural substrates may reprogram the adolescent brain and make it more susceptible to the later use of other illicit drugs, such as cocaine. However, other groups found that prior treatment with either the main psychoactive constituent of cannabis or WIN had no effect on behavioral responses to amphetamine in either adolescence or adulthood.
However, in the study by Ellgren et al., cannabinoid exposure lasted only 5 days, the doses of cannabinoid were low, and the animals were injected only once per day. A major limitation of these preclinical studies is the use of an animal model of cocaine exposure that reflects neither the direct acquisition of cocaine use nor the compulsive nature of cocaine use disorder . To address this issue, we tested the effect of adolescent exposure to the cannabinoid receptor agonist WIN on key addiction-related behaviors using a more complex animal model of drug addiction. Te model included measures of irritability-like behavior, which has recently been used as a measure of the negative emotional state in animal models of addiction. We also assessed cocaine-induced locomotion in adolescence and adulthood and the acquisition of cocaine self-administration under conditions of short access and long access in adulthood. Te long-access model represents a comprehensive model of human addiction because it produces the escalation of cocaine intake that is associated with the emergence of negative emotional states and compulsive-like responding despite adverse consequence.All behavioral testing was conducted during the dark phase. To test irritability-like behavior after WIN exposure, we used the bottle-brush test, based on the experimental method that was designed previously for mice and slightly modified to better monitor rat behavior. Currently, this model is increasingly used by both our laboratory and others as a measure of negative emotional states in animal models of addiction. This method has advantages over other behavioral paradigms that measure aggressive/ defensive behaviors, such as the social dominance/subordination paradigms and resident/intruder confrontation paradigm, because the experimenter has greater control over the mechanical stimulus and thus better precision in ensuring uniform provocation. Furthermore, the “social” factor in eliciting agonistic behavior and the risk of physical injury during an agonistic encounter are both circumvented in the bottle-brush test. Te mechanical stimulus of the moving bottle-brush has also been found to be more effective in provoking these behaviors compared with either deceased or stuffed animals. In the present study,hydroponic racks the animals were randomized, and three trained observers scored the rats’ behaviors in real-time as described below. Te observers were blinded to treatment of the animals. Testing consisted of ten 10-s trials with 10-s intertrial intervals in plastic cages with clean bedding. A bottle-brush was rotated rapidly toward the rat’s whiskers. Both aggressive responses and defensive responses were recorded. Te behavioral responses were chosen based on Riittinen et al. and Lagerspetz and Portin. Total aggressive and defensive scores were calculated for each animal based on the average score of the observers. Both aggressive and defensive behaviors were summed to calculate the total irritability score. Irritability-like behavior reflects a composite measure of aggressive vs. defensive responses. Irritability-like behavior was assessed 6 days after the last injection of WIN/vehicle in adolescence and again in adulthood 18h into withdrawal after the escalation of cocaine self-administration .
Locomotor stimulation by acute cocaine administration was assessed in rats with prior exposure to either vehicle or WIN. Tis test was performed in adolescence to model the previous finding of WIN-induced cocaine cross-sensitization in adolescence and again in adulthood . After 30min habituation to the acrylic experimental chamber , the rats were injected with cocaine , and locomotor activity was recorded for 40min under red light. Locomotor activity was recorded as the distance traveled using a video camera that was connected to the ANY-maze Video Tracking System 5.11 .Te rats were anesthetized by isofurane inhalation, and intravenous catheters were aseptically inserted in the right jugular vein using a modified version of a procedure that was described previously. Te right jugular vein was punctured with a 22-gauge needle, and the tubing was inserted and secured inside the vein by tying the vein with suture thread. Te catheter assembly consisted of an 18 cm length of MicroRenathane tubing that was attached to a guide cannula . Te guide cannula was bent at a near right angle, embedded in dental acrylic, and anchored with a mesh . Te catheter exited through a small incision on the back, and the base was sealed with a small plastic cap and metal cover cap. Te catheters were fushed daily with heparinized saline in 0.9% bacteriostatic sodium chloride that contained 20mg/0.2ml of the antibiotic Cefazolin .Self-administration in adulthood was performed in operant conditioning chambers that were enclosed in lit, sound-attenuating, ventilated environmental cubicles. Te front door and back wall of the chambers were constructed of transparent plastic, and the other walls were opaque metal. Each chamber was equipped with two retractable levers that were located on the front panel. Cocaine was delivered through plastic catheter tubing that was connected to an infusion pump, which was activated by responses on the right lever. Responses on the lef lever were recorded but did not have any scheduled consequences. Activation of the pump resulted in the delivery of 0.1 ml of cocaine . A computer controlled fluid delivery and behavioral data recording. Te rats were first trained to self-administer cocaine under a fixed-ratio 1 schedule of reinforcement in daily 1-h sessions. Each active lever press resulted in the delivery of one cocaine dose. A 20-s timeout period followed each cocaine infusion. During the TO period, responses on the active lever did not have scheduled consequences. Tis TO period occurred concurrently with illumination of a cue light that was located above the active lever to signal delivery of the positive reinforcement. Te rats were trained to self-administer cocaine in 14 sessions until a stable baseline of reinforcement was achieved . Te criterion for the acquisition of cocaine self-administration was defined as the intake of at least 2.5 mg/kg cocaine in the 1-h self-administration session, requiring at least five lever presses. This criterion was adapted from previous publications. After the 14-session acquisition period, the rats were subjected to fourteen 6-h cocaine self-administration sessions to allow them to escalate their cocaine intake. To study the motivation to seek cocaine, a progressive-ratio schedule of reinforcement was used, in which the response requirement began at one lever press/infusion and increased exponentially according to the following equation: lever presses/infusion=[5×e] − 5. Te session duration was limited to 6h or ended when a rat failed to achieve the response requirement within 1h. Te PR sessions were conducted after the training/acquisition phase and again after a stable level of escalation was achieved. In the course of the experiment, which lasted for more than 3 months, some rats were excluded at different stages of the experiment.