Neuronal substrates of relapse to cocaine-seeking behavior: role of prefrontal cortex

The return to drug seeking, even after prolonged periods of abstinence, is a defining feature of cocaine addiction. The neural circuitry underlying relapse has been identified in neuropharmacological studies of experimental animals, typically rats, and supported in brain imaging studies of human addicts. Although the nucleus accumbens (NAcc), which has long been implicated in goal-directed behavior, plays a critical role in this circuit, the prefrontal cortex (PFC) appears to process the events that directly trigger relapse: exposure to acute stress, cues previously associated with the drug, and the drug itself. In this paper, we review animal models of relapse and what they have revealed about the mechanisms underlying the involvement of the NAcc and PFC in cocaine-seeking behavior. We also present electrophysiological data from PFC illustrating how the hedonic, motor, motivational, and reinforcing effects of cocaine can be analyzed at the neuronal level. Our preliminary findings suggest a role for PFC in processing information related to cocaine seeking but not the hedonic effects of the drug. Further use of this recording technology can help dissect the functions of PFC and other components of the neural circuitry underlying relapse.     

Relative reinforcing effects of different oral ethanol doses in rhesus monkeys

The relative reinforcing effects of different doses of orally delivered ethanol were evaluated. Mouth-contact responding by rhesus monkeys was measured under concurrent fixed-ratio fixed-ratio schedules of liquid delivery (0.67 ml/delivery) from each of two spouts during daily 3-hr sessions. Experiment 1 examined persistence of responding with ethanol (2%, 8%, and 32% wt/vol) and water available. When fixed-ratio values from 8 to 128 were tested, the number of ethanol deliveries obtained per session decreased as the response requirement increased. The decrease in deliveries was less at higher than at lower ethanol concentrations, however. Experiment 2 examined choice between two ethanol concentrations under concurrent fixed-ratio 16 schedules (4% vs. 8%, 4% vs. 16%, 8% vs. 16%, 2% vs. 8%, 2% vs. 32%, 8% vs. 32%). Higher concentrations (16%, 32%) generally maintained more responding than concurrently available concentrations of 8% or less. An exception was the observation of a preference for 8% over 32% ethanol. When the fixed-ratio value was increased, however, the relative preference for these two doses was reversed so that 32% ethanol maintained more responding than 8% ethanol. Thus, the direction of the preference depended on the size of the response requirement. These results indicate that the reinforcing effects of ethanol increase with dose.     

Limbic-striatal memory systems and drug addiction

Drug addiction can be understood as a pathological subversion of normal brain learning and memory processes strengthened by the motivational impact of drug-associated stimuli, leading to the establishment of compulsive drug-seeking habits. Such habits evolve through a cascade of complex associative processes with Pavlovian and instrumental components that may depend on the integration and coordination of output from several somewhat independent neural systems of learning and memory, each contributing to behavioral performance. Data are reviewed that help to define the influences of conditioned Pavlovian stimuli on goal-directed behavior via sign-tracking, motivational arousal, and conditioned reinforcement. Such influences are mediated via defined corticolimbic-striatal systems converging on the ventral striatum and driving habit-based learning that may depend on the dorsal striatum. These systems include separate and overlapping influences from the amygdala, hippocampus, and cingulate and medial prefrontal cortex on drug-seeking as well as drug-taking behavior, including the propensity to relapse.     

Three predictions of the economic concept of unit price in a choice context

Economic theory makes three predictions about consumption and response output in a choice situation: (a) When plotted on logarithmic coordinates, total consumption (i.e., summed across concurrent sources of reinforcement) should be a positively decelerating function, and total response output should be a bitonic function of unit price increases; (b) total consumption and response output should be determined by the value of the unit price ratio, independent of its cost and benefit components; and (c) when a reinforcer is available at the same unit price across all sources of reinforcement, consumption should be equal between these sources. These predictions were assessed in human cigarette smokers who earned cigarette puffs in a two-choice situation at a range of unit prices. In some sessions, smokers chose between different amounts of puffs, both available at identical unit prices. Individual subjects' data supported the first two predictions but failed to support the third. Instead, at low unit prices, the relatively larger reinforcer (and larger response requirement) was preferred, whereas at high unit prices, the smaller reinforcer (and smaller response requirement) was preferred. An expansion of unit price is proposed in which handling costs and the discounted value of reinforcers available according to ratio schedules are incorporated.     

Effects of compounding drug-related stimuli: escalation of heroin self-administration

Previous experiments have demonstrated that presenting independently established discriminative stimuli in compound can substantially increase operant responding maintained by food reinforcement or shock avoidance. Recently, this phenomenon was also shown to occur with cocaine self-administration. The present study further assessed the generality of these stimulus-compounding effects by systematically replicating them with heroin self-administration. Rats' nose-poke responses produced intravenous heroin (0.025 mg/kg per infusion) on a variable-ratio schedule when either a tone or a light was present. In the absence of these stimuli, responding was not reinforced. Once discriminative control by the tone and light had been established, the stimuli were presented in compound under extinction (with heroin discontinued) or maintenance conditions (with heroin available during test-stimulus presentations). In extinction, the tone-light compound increased responding approximately threefold compared to tone or light alone. Under maintenance conditions, compounding increased heroin intake approximately twofold. These effects closely matched those obtained earlier with cocaine. This consistency across pharmacological classes and across drug and nondrug reinforcers further confirms that (a) self-administered drugs support conditioning and learning in a manner similar to that supported by other reinforcers; and (b) multiple drug-related cues interact in lawful and predictable ways to affect drug seeking and consumption.     

Drug discrimination: stimulus control during repeated testing in extinction

Rats were trained, under a two-lever drug-discrimination procedure, to respond differentially depending upon whether lorazepam (1.0 mg/kg) or no injection had been administered before the session. Responses on the appropriate lever produced a food pellet under a modified fixed-ratio (FR) 10 schedule, in which the 10 responses had to be emitted consecutively. In reinforcement tests, completing an FR 10 on either lever produced a pellet. In extinction tests, stimulus changes paired with reinforcement occurred but no pellet was delivered. Training sessions were conducted between test sessions. Each of four extinction phases consisted of six tests preceded by one stimulus (e.g., lorazepam). Repeated exposures to extinction reduced response rates for all rats, but stimulus control, as inferred from either percentage of total responses or percentage of total FR 10s on the drug-appropriate lever, remained high. The percentage of total FR 10s measure was less subject to skewing under low-rate conditions than was the percentage of total responses measure and provided an evaluation of stimulus control in terms of meeting the consecutive response contingency. These results demonstrate a level of independence between response rate and stimulus control in drug discrimination, which has positive implications for the validity of interpreting discriminative effects of novel test conditions in well-trained animals, even when overall response rates are low.     

Materialism Moderates the Effect of Accounting for Time on Prosocial Behaviors

Accounting for time is defined as putting a price on time. Researchers have demonstrated that accounting for time reduces the time individuals spend on others; however, its association with monetary donations has not been examined. We hypothesized that accounting for time will activate a utility mindset that would affect one’s allocation of time and money. In Study 1, the mediating effect of utility mindsets on the relationship between accounting for time and prosocial behavior was examined. In Study 2, we examined the effect of accounting for time on time spent helping and donating money, and the moderating role of material values on the relationship between accounting for time and prosocial behavior. Results showed that accounting for time activated a mindset of utility maximization that, in turn, reduced participants’ prosocial behavior; moreover, materialism moderated the effect of accounting for time on prosocial behavior.     

O'NEILL'S JOURNEY

This paper considers some of the processes through which Eugene O'Neill (1888–1953) dramatically shaped his inner life and through which he created his plays. These processes at their finest are evident in his composition of Long Day's Journey into Night (1941a). During its 21‐month composition, the play went through three different versions, as evidenced by the playwright's handwritten and typed materials (O'Neill, unpublished, a, b, c, d). This paper posits that each version reflects O'Neill's changing state of mind as he began to master his instinctual life, developing increasingly rich characters and creating a painful, deeply tragic vision. Thus, this paper shows that O'Neill's great artistic achievement reflected a great psychological one.     

Double Reference Points: the Effects of Social and Financial Reference Points on Decisions Under Risk

The existing literature is inconsistent about how social comparison affects risk attitudes. We propose a framework where the total utility is composed of the social and financial utilities. The financial utility is consistent with prospect theory (i.e., an S‐shaped utility function with a financial reference point), whereas the social utility is affected by both social and financial reference points. Therefore, social risk attitudes are determined by interaction between gains/losses in both social and financial contexts. On the basis of safety‐first principle, we propose that when experiencing financial gains, individuals tend to seek upside potential and take social risks (i.e., a convex social utility function). In contrast, when facing financial losses, people would be more risk seeking in social gains but more risk averse in social losses to maximize security (i.e., an inverse S‐shaped utility function). We also propose that the relative importance of financial and social utilities depends on the saliency of the reference points and size of stakes. Studies 1 and 2 showed that individuals were risk seeking in both social gains and losses with social reference points alone. Studies 3 and 4 demonstrated that when both financial and social reference points were salient, participants were risk averse in both social gains and losses when facing financial gains, but risk seeking in social gains and risk averse in social losses when facing financial losses. The hypotheses derived from the theoretical framework were in general supported by our experiments. Copyright © 2015 John Wiley & Sons, Ltd.