Evidence of individual differences in motives for nicotine seeking in classical nicotine self-administration and associated outcomes of varenicline administration

Background Smokers vary in their motives for tobacco seeking, suggesting that they could benefit from personalized treatments. However, these variations have received little attention in animal models for the study of tobacco dependence. In the most classically used model, ie. intravenous self-administration of nicotine in the rat, seeking behaviour is reinforced by the combination of intravenous nicotine with a discrete stimulus (eg. discrete cue light). In both human and animals, two types of psychopharmacological interactions between nicotine and environmental stimuli have been evidenced. Whether these two types of interactions contribute equally to nicotine seeking in all individuals is unknown. Methods We combined behavioural pharmacology and clustering analysis. In an outbred male rat population, we tested whether nicotine and the discrete nicotine-associated cue light contributed equally to self-administration in all individuals. Two clusters of rats were identified, in which we further studied the nature of the psychopharmacological interaction between nicotine and the cue, as well as the response to the cessation aid varenicline when nicotine was withdrawn. Results Notably, withdrawing nicotine produced drastic opposed effects on seeking behavior in the two identified clusters of rats; a 50% increase vs a 18% decrease, respectively. The first cluster of rats sought for the primary reinforcing effects of nicotine and the discrete cue light that has gained nicotine-like secondary reinforcing properties. The second cluster sought nicotine for its ability to enhance the primary reinforcing effects of the discrete cue light. Critically, the approved cessation aid Varenicline counteracted the absence of nicotine in both, but eventually decreasing seeking in the former but increasing it in the latter. Conclusions Classical rodent models for the study of the reinforcing and addictive effects of nicotine hide individual variations in the psychopharmacological motives supporting seeking behavior. These variations may be a decisive asset for improving their predictive validity in the perspective of precision medicine for smoking cessation.

Moisture absorption behavior of hybrid bionanocomposites of polylactic acid and evaluation of physicochemical properties

The current study details on the moisture absorption behavior and its effect on the hybrid bionanocomposites of polylactic acid (PLA). In order to improve the compatibility between PLA and fiber, silanization was performed on fiber as well as C30B nanoclay was used as the secondary reinforcing filler. Silanization was confirmed through Fourier transform infrared study. In addition, thermogravimetric analysis (TGA) of fiber proved that hydrophilicity of fiber could decrease after silane treatment. Bionanocomposites of PLA were prepared using melt blending technique followed by injection molding. Samples were immersed in distilled water for 30 days at room temperature to analyze the moisture absorption behavior and its kinetic parameter. The results from moisture study revealed that PLA/fiber/nanoclay bionanocomposites have higher moisture resistance than PLA/fiber biocomposites. Further, the changes in mechanical as well as thermal properties of PLA and its composites during moisture absorption have been carried out. With increase in percentage of moisture absorption, the mechanical strength and modulus of composites decreased significantly, however, the unnotched impact strength and elongation at break found to improve. TGA of PLA and its composites revealed that thermal stability of composites decreased after moisture absorption. The morphology of the composites was monitored during moisture absorption, and the result revealed that moisture absorption has severely damaged the matrix–fiber interface.

Learning of Object-Object Associations by Monkeys

Monkeys were trained in tasks where stimulus objects were presented in pairs, one object of a pair concealing the other, and the monkeys had to displace the top object followed by the bottom object in order to obtain a food reward. In two experiments it was demonstrated that under these conditions the animals formed object-object associations such that the top object recalled in memory the bottom object that had previously been found underneath it. The monkeys were able to discriminate in recall between bottom objects that were identical in secondary reinforcing value and differed only in colour.

Primary and Secondary Motivational Properties of a Light Stimulus

Rats were trained on a continuous reward schedule (CRF) in a 2-bar test box with or without light contingency associated with food reward. During extinction trials with the light contingency presented on CRF, the light contingency was shown to facilitate extinction on the basis of response totals (energizing effect) and percentage of responses on the reward bar (directional effect). For these extinction trials, no evidence was obtained for secondary reinforcing (Sr) properties of the light contingency. However, a second experiment found a strong Sr energizing effect when the light contingency was presented on a FR-5 or FR-10 schedule during extinction trials. These energizing effects were also obtained for rats trained without the light contingency, but to a lesser degree than for rats trained with the light contingency. Presentation of the light contingency on a FR schedule during extinction trials also resulted in a strong directional effect for all groups, regardless of the training condition. A moderately durable energizing effect of Sr was obtained which was an increasing function of partial periodic Sr during extinction trials.

Delay of Shock-Escape with and without Stimulus Change

Effects of a stimulus change presented with delay of shock-escape were examined in escape conditioning. Where a stimulus change occurred with the delay, greater response rates were found before delay and lower rates during the delay. Results are interpreted as providing evidence for the efficacy of a stimulus change in maintaining behavior with delay of negative reinforcement. Results are consistent with an information account of secondary reinforcement. Data from a control procedure suggest the possibility that stimuli paired with shock termination might have two opposite properties, secondary reinforcing and conditioced aversive, depending upon the background stimulus conditions prevailing at testing.