Extinction Of Conditioned Behavior Research Articles

A sphingolipid mechanism for behavioral extinction.

Reward-dependent instrumental behavior must continuously be re-adjusted according to environmental conditions. Failure to adapt to changes in reward contingencies may incur psychiatric disorders like anxiety and depression. When an expected reward is omitted, behavior undergoes extinction. While extinction involves active re-learning, it is also accompanied by emotional behaviors indicative of frustration, anxiety, and despair (extinction-induced depression). Here, we report evidence for a sphingolipid mechanism in the extinction of behavior. Rapid extinction, indicating efficient re-learning, coincided with a decrease in the activity of the enzyme acid sphingomyelinase (ASM), which catalyzes turnover of sphingomyelin to ceramide, in the dorsal hippocampus of rats. The stronger the decline in ASM activity, the more rapid was the extinction. Sphingolipid-focused lipidomic analysis showed that this results in a decline of local ceramide species in the dorsal hippocampus. Ceramides shape the fluidity of lipid rafts in synaptic membranes and by that way can control neural plasticity. We also found that aging modifies activity of enzymes and ceramide levels in selective brain regions. Aging also changed how the chronic treatment with corticosterone (stress) or intranasal dopamine modified regional enzyme activity and ceramide levels, coinciding with rate of extinction. These data provide first evidence for a functional ASM-ceramide pathway in the brain involved in the extinction of learned behavior. This finding extends the known cellular mechanisms underlying behavioral plasticity to a new class of membrane-located molecules, the sphingolipids, and their regulatory enzymes, and may offer new treatment targets for extinction- and learning-related psychopathological conditions. Sphingolipids are common lipids in the brain which form lipid domains at pre- and postsynaptic membrane compartments. Here we show a decline in dorsal hippocampus ceramide species together with a reduction of acid sphingomyelinase activity during extinction of conditioned behavior in rats. This reduction was associated with expression of re-learning-related behavior, but not with emotional behaviors. Read the Editorial Highlight for this article on page 485.

Why are Some Games More Addictive than Others: The Effects of Timing and Payoff on Perseverance in a Slot Machine Game.

Manipulating different behavioral characteristics of gambling games can potentially affect the extent to which individuals persevere at gambling, and their transition to problematic behaviors. This has potential impact for mobile gambling technologies and responsible gambling interventions. Two laboratory models pertinent to this are the partial reinforcement extinction effect (PREE) and the trial spacing effect. Both of these might speed up or delay the acquisition and extinction of conditioned behavior. We report an experiment that manipulated the rate of reinforcement and inter trial interval (ITI) on a simulated slot machine where participants were given the choice between gambling and skipping on each trial, before perseverative gambling was measured in extinction, followed by measurements of the illusion of control, depression and impulsivity. We hypothesized that longer ITI’s in conjunction with the low rates of reinforcement observed in gambling would lead to greater perseverance. We further hypothesized, given that timing is known to be important in displaying illusory control and potentially in persevering in gambling, that prior exposure to longer intervals might affect illusions of control. An interaction between ITI and rate of reinforcement was observed, as low reinforced gamblers with a long ITI gambled for longer. Respondents also displayed extinction and a PREE. Gamblers exposed to a higher rate of reinforcement gambled for longer in acquisition. Impulsivity was associated with extended perseverance in extinction, and more depressed gamblers in the high reinforcement short ITI group persevered for longer. Performance in the contingency judgment failed to support the second hypothesis: the only significant contrast observed was that participants became better calibrated as the task progressed.

Effects of ACTH-Analogues on Extinction of Conditioned Behavior

Adrenocorticotropic hormone (ACTH) and corticosteroids exhibit an opposite effect on extinction of conditioned behavior in studies that were designed to elucidate the roles of the separate hormones: ACTH can inhibit extinction of conditioned avoidance behavior, while glucocorticosteroids—and some other steroids as well—can facilitate the rate of extinction. The study of the effects of ACTH on the behavior of intact animals received a new impetus after the discovery that fragments of this hormone containing the first 10 amino acids—or even smaller peptides such as ACTH-(C10)—could still exhibit a similar behavioral effect as ACTH. These peptides lack the well-known biological activities of the intact hormone such as stimulation of the adrenals. The behavioral effect of ACTH could be studied in intact animals independently of concomitant steroid action. Labeling these peptides as “ACTH-analogues” is more a matter of habit than of precise description because α- and β -melanocyte stimulating hormone (MSH), which exert a similar inhibiting effect on extinction of conditioned avoidance behavior as ACTH, also share the amino acid sequence that is known as ACTH.