A review of preclinical research demonstrating that drug and non-drug reinforcers differentially affect behavior.

This review describes and summarizes current preclinical research revealing important differences between drug and non-drug reinforcers in terms of their effects on behavior. Despite research showing that drugs are not especially strong reinforcers in animals, a number of other behavioral differences potentially relevant to addiction have been reported in studies that have compared drug and non-drug reinforcers. Several of these effects appear only after long-term access to drugs. These include an escalation of drug intake, an increased persistence in responding for the drug, and a decreased sensitivity to the effects of punishers or other suppressors of drug seeking. Further differences between drug and non-drug reinforcers include the effects that reinforcer-paired stimuli have on behavior. Drug cues, as compared to food cues, have been shown to exert greater control over reinforcer-seeking behavior after periods of abstinence. Similarly, behavior previously reinforced by drugs, but not food, has been shown to be susceptible to stress-induced reinstatement after extinction. The behavioral differences between drug and non-drug reinforcers reviewed here may identify special features of drugs that lead to addiction.

The effects of light cycle phase on morphine-induced conditioned taste aversions in the Lewis, Fischer and Sprague-Dawley rat strains.

The present experiment investigated the effect of light cycle phase on morphine-induced conditioned taste aversions in the Lewis (LEW), Fischer (F344) and Sprague-Dawley (SD) rat strains. Separate groups of rats from each strain were trained during either the light phase or the dark phase on a procedure in which saccharin was paired with one of two doses of morphine (or vehicle). With 3.2mg/kg morphine, strain differences were observed during the light phase, with F344 rats displaying a significantly stronger taste aversion than the LEW rats, who displayed a significantly stronger aversion than the SD rats. In contrast, during the dark phase, 3.2mg/kg morphine produced comparable, moderately strong aversions in all strains. With 10.0mg/kg morphine, F344 rats developed stronger aversions than either the LEW or SD rats in both phases of the light cycle. The effect of light cycle was most clearly seen in the SD rats, where stronger aversions were produced in the dark phase for both morphine doses. For the LEW rats, stronger aversions were produced in the dark as compared to the light only with the low dose of morphine. For the F344 rats, aversions of comparable strength were observed in both phases of the light cycle for both morphine doses. The finding that light cycle differentially affects morphine-induced taste aversions in these strains is consistent with what is known about strain differences in circadian patterns of corticosterone activity and with previous results relating corticosterone to morphine-induced taste aversions.

A comparison of Lewis and Fischer rat strains on autoshaping (sign-tracking), discrimination reversal learning and negative auto-maintenance.

Lewis (LEW) and Fischer (F344) rat strains differ on a number of physiological characteristics, such as hypothalamic-pituitary-adrenal (HPA) axis activity, as well as on behavioral tasks, including those that measure impulsivity and drug reward. Since autoshaping, the phenomenon where animals approach and contact reward-paired conditioned stimuli, has been linked to HPA axis functioning, impulsivity and drug taking, the present study compared LEW and F344 rats on the rate of acquisition and performance of the autoshaping response. Rats were trained on an autoshaping procedure where insertions of one retractable lever (CS(+)) were paired response-independently with food, while insertions of another lever (CS(-)) were not paired with food. LEW rats acquired the autoshaping response more rapidly and also performed the autoshaping response at a higher rate than F344 rats. No differences between the strains were observed when rats were trained on a discrimination reversal where the CS(+) and CS(-) levers were reversed or during a negative auto-maintenance phase where CS(+) lever contacts cancelled food delivery. Potential physiological mechanisms that might mediate the present results, including strain differences in HPA axis and monoamine neurotransmitter activity, are discussed. The finding that LEW (as compared to F344 rats) more readily acquire autoshaping and perform more responses is consistent with research indicating that LEW rats behave more impulsively and more readily self-administer drugs of abuse.

Maternal behavior in F344/N and LEW/N rats. Effects on carrageenan-induced inflammatory reactivity and body weight.

Inbred Fischer (F344/N) and Lewis (LEW/N) rats differ on a myriad of behavioral and physiological endpoints, such as inflammatory, startle and drug responsivity. These differences point to underlying genetic differences between the strains. However, genetic models of hypertension have shown the importance of the maternal environment in the development of high blood pressure, suggesting that maternal influences might also play a role in adult phenotypes of the LEW/N and F344/N strains. This was tested in the present series of experiments in which the effects of crossfostering on carrageenan-induced inflammation and on body weight were examined in the two strains. Following the demonstration that the two strains differed in maternal behavior (Experiment 1), which was independent of the pup being reared (Experiment 2), crossfostered and in-fostered pups from the LEW/N and F344/N strains were injected with carrageenan (at 60 days of age) and subsequently assessed for the accumulation of exudate in response to the injection. Body weights were also monitored from birth through 60 days of age. Although crossfostering affected body weight of the two strains, specifically, reducing weights in LEW/N pups reared by F344/N dams and increasing weights of F344/N pups reared by LEW/N dams, crossfostering did not affect inflammatory reactivity to carrageenan. Specifically, LEW/N pups had a greater level of exudate than F344/N pups, independent of the conditions under which they were reared, suggesting that differences in the inflammatory response between these two strains are under a high degree of genetic control. These results were discussed in terms of genetic factors mediating the early form of immune reactivity induced by carrageenan.