Exposure to an enriched environment reduces alcohol self-administration in Sardinian alcohol-preferring rats.

Living in an enriched environment (EE) produces a notable impact on several rodent behaviors, including those motivated by drugs of abuse. This picture is somewhat less clear when referring to alcohol-motivated behaviors. With the intent of contributing to this research field with data from one of the few rat lines selectively bred for excessive alcohol consumption, the present study investigated the effect of EE on operant oral alcohol self-administration in Sardinian alcohol-preferring (sP) rats. Starting from Postnatal Day (PND) 21, male sP rats were kept under 3 different housing conditions: impoverished environment (IE; single housing in shoebox-like cages with no environmental enrichment); standard environment (SE; small colony cages with 3 rats and no environmental enrichment); EE (large colony cages with 6 rats and multiple elements of environmental enrichment, including 2 floors, ladders, maze, running wheels, and shelter). From PND 60, rats were exposed to different phases of shaping and training of alcohol self-administration. IE, SE, and EE rats were then compared under (i) fixed ratio (FR) 4 (FR4) schedule of alcohol reinforcement for 20 daily sessions and (ii) progressive ratio (PR) schedule of alcohol reinforcement in a final single session. Acquisition of the lever-responding task (shaping) was slower in EE than IE and SE rats, as the likely consequence of a "devaluation" of the novel stimuli provided by the operant chamber in comparison to those to which EE rats were continuously exposed in their homecage or an alteration, induced by EE, of the rat "emotionality" state when facing the novel environment represented by the operant chamber. Training of alcohol self-administration was slower in EE than IE rats, with SE rats displaying intermediate values. A similar ranking order (IE>SE>EE) was also observed in number of lever-responses for alcohol, amount of self-administered alcohol, and breakpoint for alcohol under FR4 and PR schedules of reinforcement. These data suggest that living in a complex environment reduced the reinforcing and motivational properties of alcohol in sP rats. These results are interpreted in terms of the reinforcing and motivational properties of the main components of EE (i.e., social interactions, physical activities, exploration, novelty) substituting, at least partially, for those of alcohol.

Image-Based Monitoring of Cracks: Effectiveness Analysis of an Open-Source Machine Learning-Assisted Procedure.

The proper inspection of a cracks pattern over time is a critical diagnosis step to provide a thorough knowledge of the health state of a structure. When monitoring cracks propagating on a planar surface, adopting a single-image-based approach is a more convenient (costly and logistically) solution compared to subjective operators-based solutions. Machine learning (ML)- based monitoring solutions offer the advantage of automation in crack detection; however, complex and time-consuming training must be carried out. This study presents a simple and automated ML-based crack monitoring approach implemented in open sources software that only requires a single image for training. The effectiveness of the approach is assessed conducting work in controlled and real case study sites. For both sites, the generated outputs are significant in terms of accuracy (~1 mm), repeatability (sub-mm) and precision (sub-pixel). The presented results highlight that the successful detection of cracks is achievable with only a straightforward ML-based training procedure conducted on only a single image of the multi-temporal sequence. Furthermore, the use of an innovative camera kit allowed exploiting automated acquisition and transmission fundamental for Internet of Things (IoTs) for structural health monitoring and to reduce user-based operations and increase safety.

Chronic Red Bull Consumption during Adolescence: Effect on Mesocortical and Mesolimbic Dopamine Transmission and Cardiovascular System in Adult Rats.

Energy drinks are very popular nonalcoholic beverages among adolescents and young adults for their stimulant effects. Our study aimed to investigate the effect of repeated intraoral Red Bull (RB) infusion on dopamine transmission in the nucleus accumbens shell and core and in the medial prefrontal cortex and on cardiac contractility in adult rats exposed to chronic RB consumption. Rats were subjected to 4 weeks of RB voluntary consumption from adolescence to adulthood. Monitoring of in vivo dopamine was carried out by brain microdialysis. In vitro cardiac contractility was studied on biomechanical properties of isolated left-ventricular papillary muscle. The main finding of the study was that, in treated animals, RB increased shell dopamine via a nonadaptive mechanism, a pattern similar to that of drugs of abuse. No changes in isometric and isotonic mechanical parameters were associated with chronic RB consumption. However, a prolonged time to peak tension and half-time of relaxation and a slower peak rate of tension fall were observed in RB-treated rats. It is likely that RB treatment affects left-ventricular papillary muscle contraction. The neurochemical results here obtained can explain the addictive properties of RB, while the cardiovascular investigation findings suggest a hidden papillary contractility impairment.

Suppressing effect of saikosaponin A, an active ingredient of Bupleurum falcatum, on chocolate self-administration and reinstatement of chocolate seeking in rats.

Recent lines of experimental evidence have indicated that saikosaponin A (SSA) - a bioactive ingredient of the medicinal plant, Bupleurum falcatum L. - suppressed alcohol, morphine, and cocaine self-administration in rats. The present paper was designed to assess whether the protective properties of SSA on addiction-related behaviors generalize to a hyperpalatable food such as a chocolate-flavored beverage (CFB). To this end, rats were initially trained to lever-respond for CFB [5% (w/v) Nesquik® powder in water] under fixed ratio (FR) 10 (FR10) schedule of reinforcement. Once lever-responding reached stable levels, rats were treated acutely with two different dose ranges of SSA (0, 0.25, 0.5, and 1mg/kg; 0, 1, 2.5, and 5mg/kg; i.p.) and exposed to the FR10 and progressive ratio (PR) schedules of reinforcement in four independent experiments. The effect of acutely administered SSA (0, 0.25, 0.5, and 1mg/kg; i.p.) on cue-induced reinstatement of seeking behavior for CFB was also assessed. Under the FR and PR schedules of reinforcement, treatment with SSA diminished lever-responding for CFB, amount of self-administered CFB, and breakpoint for CFB. All variables were virtually completely suppressed after treatment with 5mg/kg SSA. Treatment with SSA also suppressed reinstatement of CFB-seeking behavior. No dose of SSA altered rat motor-performance, evaluated exposing all rats to an inverted screen test immediately after the self-administration session. These results demonstrate that acute treatment with SSA potently suppressed several addictive-like behaviors motivated by highly hedonic nourishment. These data extend to a highly rewarding natural stimulus the anti-addictive properties of SSA recently disclosed in rats self-administering alcohol, morphine, and cocaine.

Elevated reinforcing and motivational properties of alcohol at the end of the nocturnal period in sP rats.

RATIONALE: Sardinian alcohol-preferring (sP) rats displayed high sensitivity to time schedule and consumed intoxicating amounts of alcohol during the last portion of the dark phase of the light/dark cycle when exposed to daily drinking sessions of 1 h, with concurrent availability of multiple alcohol concentrations and unpredictability of time of alcohol access. OBJECTIVES: The present study investigated whether sensitivity of sP rats to time schedule extended to operant procedures of alcohol self-administration. METHODS: In experiment 1, three different alcohol solutions (10, 20, and 30%, v/v) were concurrently available under a fixed ratio 4 schedule of reinforcement and with unpredictable time schedule; water was available uncontingently. Experiments 2 and 3 assessed the sensitivity of the motivational properties of alcohol to time schedule; rats were exposed to (a) self-administration sessions under the progressive ratio (PR) schedule of reinforcement and (b) sessions of alcohol seeking under the extinction responding (ER) schedule. RESULTS: In experiment 1, number of lever responses and amount of self-administered alcohol were positively correlated with time of alcohol access during the dark phase. When the self-administration session occurred at the first and latest hours of the dark phase, the amount of self-administered alcohol averaged 0.95-1.0 and 1.55-1.65 g/kg, respectively. In experiments 2 and 3, values of breakpoint and ER for alcohol were approximately 50% higher when the sessions occurred at the last than first hour of the dark phase. CONCLUSIONS: The reinforcing and motivational properties of alcohol were sensitive to time schedule and stronger at the end of the dark phase.

Comparison of the effect of the GABAΒ receptor agonist, baclofen, and the positive allosteric modulator of the GABAB receptor, GS39783, on alcohol self-administration in 3 different lines of alcohol-preferring rats.

BACKGROUND: Administration of the GABA(B) receptor agonist, baclofen, and positive allosteric modulator, GS39783, has been repeatedly reported to suppress multiple alcohol-related behaviors, including operant oral alcohol self-administration, in rats. This study was designed to compare the effect of baclofen and GS39783 on alcohol self-administration in 3 lines of selectively bred, alcohol-preferring rats: Indiana alcohol-preferring (P), Sardinian alcohol-preferring (sP), and Alko Alcohol (AA). METHODS: Rats of each line were initially trained to respond on a lever, on a fixed ratio (FR) 4 (FR4) schedule of reinforcement, to orally self-administer alcohol (15%, v/v) in daily 30-minute sessions. Once responding reached stable levels, rats were exposed to a sequence of experiments testing baclofen (0, 1, 1.7, and 3 mg/kg; i.p.) and GS39783 (0, 25, 50, and 100 mg/kg; i.g.) on FR4 and progressive ratio (PR) schedules of reinforcement. Finally, to assess the specificity of baclofen and GS39783 action, rats were slightly food-deprived and trained to lever-respond for food pellets. RESULTS: The rank of order of the reinforcing and motivational properties of alcohol was P>sP>AA rats. Under both FR and PR schedules of reinforcement, the rank of order of potency and efficacy of baclofen and GS39783 in suppressing alcohol self-administration was P>sP>AA rats. Only the highest dose of baclofen reduced lever-responding for food pellets; this effect was common to all 3 rat lines. Conversely, no dose of GS39783 altered lever-responding for food in any rat line. CONCLUSIONS: These results suggest that: (i) the strength of the reinforcing and motivational properties of alcohol differ among P, sP, and AA rats; (ii) the reinforcing and motivational properties of alcohol in P, sP, and AA rats are differentially sensitive to treatment with baclofen and GS39783; (iii) the heterogeneity in sensitivity to baclofen and GS39783 of alcohol self-administration in P, sP, and AA rats may resemble the differential effectiveness of pharmacotherapies among the different typologies of human alcoholics; and (iv) the GABA(B) receptor is part of the neural substrate mediating the reinforcing and motivational properties of alcohol.

Enhancement of shortening velocity, power, and acto-myosin crossbridge (CB) kinetics following long-term treatment with propionyl-L-carnitine, coenzyme Q10, and omega-3 fatty acids in BIO TO-2 cardiomyopathic Syrian hamsters papillary muscle.

Impaired functions of myocardial muscle cells in human and animals, is a primary defect associated with idiopathic dilated cardiomyopathy (DCM). The pathophysiological mechanisms implicated in the DCM are yet to be clarified and an effective therapy is still not available. The BIO TO-2 cardiomyopathic Syrian Hamsters (CMSHs) represent an animal model of idiopathic DCM. The aim of this study was to investigate the effect of long-term treatment (2 months) with propionyl-L-carnitine (PLC), coenzyme Q(10), omega-3 fatty acids and a combination of these three agents (formulation HS12607) on mechanical properties and acto-myosin crossbridges (CBs) kinetics of left ventricular (LV) papillary muscle from control and treated 10 month old BIO TO-2 CMSHs. Isometric and isotonic contractile properties of isolated papillary muscle from control and treated CMSHs were investigated, and acto-myosin CB number, force and kinetics were calculated using Huxley's equations. Mechanical parameter values were higher in treated than in control hamsters, particularly when substances were administered together in a coformulation (HS12607). Compared to control, HS12607-treated papillary muscles showed a significant increase of maximum peak isometric tension (P(o)) (30.06 +/- 4.91 vs. 19.74 +/- 5.00 mN/mm(2)), maximum extent of muscle shortening (0.13 +/- 0.03 vs. 0.07 +/- 0.02 L/L(max)), maximum unloaded shortening velocity (1.18 +/- 0.24 vs. 0.53 +/- 0.13 L/L(max) s(-1)) and maximum peak of power output (5.52 +/- 1.61 vs. 1.58 +/- 0.83). The curvature of the hyperbolic force-velocity relationships did not differ between control and treated hamsters. When compared to controls, acto-myosin CB number increased in treated hamsters [(6.67 +/- 1.91) 10(10)/mm(2) vs. (3.55 +/- 2.08) 10(10)/mm(2)], whereas the unitary force of single CB was similar in control and treated animals. The peak value of the rate constant for CB attachment (f(1)) and detachment (g(2)) was higher in treated animals when compared to control. (93.87 +/- 25.82 vs.47.28 +/- 10.88 s(-1) and 214.40 +/- 44.64 vs. 95.56 +/- 23.49 s(-1), respectively). In conclusion, the present study illustrates that supplementation with PLC, CoQ(10) and omega-3 fatty acids improved motor parameters, energetic, and CB kinetics of BIO TO-2 CMSH papillary muscle indicating that these naturally occurring substances may be a valid adjuvant to conventional therapy in DCM.