Ari P. Kirshenbaum

A quantitative review of the ubiquitous relapse curve

The primary goal of this study is to ascertain whether relapse to drug dependence, in terms of continuous abstinence assessment, exhibits a typical pattern that can be characterized by a common quantitative function. If the relapse curve is indeed ubiquitous, then some underlying mechanism must be operating to shape the curve that transcends variables such as drug class, population, or treatment type. Survival analyses are performed on 20 alcohol and tobacco treatment studies using the proportions of individuals remaining abstinent after a period of initial abstinence. Several parametric models of relapse are compared, and the results demonstrate that a log-logistic distribution is the most accurate reflection of the available data and the basic shape of the relapse curve is uniform. In most reports examined, the rate of relapse decelerates after initial abstinence has been achieved, and therefore, the amount of accumulated time abstinent may be the transcending variable that operates to shape the relapse curve.

Nicotine-induced impulsive action: sensitization and attenuation by mecamylamine.

A conjunctive variable-interval differential-reinforcement-of-low-rate (VI-DRL, n=18) responding schedule and a stop-signal task (n=18) were used to evaluate the disinhibiting effects of nicotine on response withholding in rats. Sucrose solution was used to reinforce responding, and after a stable baseline was achieved under saline-administration conditions, 0.3 mg/kg nicotine was delivered before each session. Experiment 1 showed that repeated, but not the initial, administration of nicotine decreased performance on both tasks, and the effect of sensitization followed a similar timeline; 10 consecutive doses resulted in poorer proportion-correct VI-DRL trials and percent correct stop trials than the initial dose of nicotine. Furthermore, sensitization to 0.3 mg/kg nicotine decreased performance regardless of whether a spaced or consecutive-dosing regimen was followed. Experiment 2 was designed to test whether mecamylamine hydrochloride (0.1–1.0 mg/kg) could attenuate the effects of repeated 0.3 mg/kg nicotine administration, and the degree to which mecamylamine attenuation of the effect of nicotine to produce impulsive action was relative to dose. Results from experiment 2 showed that response disinhibition, as evaluated using the VI-DRL and stop-signal tasks, is related in a systematic manner to nicotinic-acetylcholine receptor activation.

Risk-sensitive foraging in rats: the effects of response-effort and reward-amount manipulations on choice behavior.

The literature on risk-sensitive foraging theory provides several accounts of species that fluctuate between risk-averse and risk-prone strategies. The daily energy budget rule suggests that shifts in foraging strategy are precipitated by changes in the foragers energy budget. Researchers have attempted to alter the organisms energy budget using a variety of techniques such as food deprivation, manipulation of ambient temperatures, and delays to food reward; however, response-effort manipulations have been relatively neglected. A choice preparation using a wheel-running response and rats examined risk-sensitive preferences when both response effort and reward amounts were manipulated. Concurrently available reinforcement schedules (FI/60 and VI/60) yielded equivalent food amounts per unit time in all treatments. Two levels of response effort (20 or 120 g tangential resistance) and two levels of reward amount (three or nine pellets) were combined to form four distinct response-effort/reward-amount pairings. Increasing reward amounts significantly shifted choice toward the FI schedule in both response-effort conditions. The incidence of choice preference and the magnitude of shifts in choice were greater for the high response-effort conditions than for the low response-effort conditions. Implications of the significant interaction between response effort and reward amount are discussed in terms of a general energy-budget model.

Differential-reinforcement-of-low-rate-schedule performance and nicotine administration: a systematic investigation of dose, dose-regimen, and schedule requirement.

Differential-reinforcement-of-low-rate (DRL) schedules have been used to evaluate the effects of a wide variety of drugs, including amphetamines, cannabanoids, and antidepressant medication. To earn a reinforcer, organisms operating under a DRL schedule are required to withhold a response for a predetermined amount of time before responding, and therefore this schedule maintains a low rate of responding and can be viewed as a response-inhibition task. In experiment 1, three different DRL schedules (4.5, 9.5, and 29.5 s) were used to evaluate systematically a range of nicotine doses (0.0, 0.1, 0.3, and 0.5 mg/kg). The dose–response effect of nicotine then was compared with the effects of increased reinforcer magnitude on responding. Both the administration of nicotine and increased reinforcer magnitude engendered less accurate DRL-schedule performance compared with baseline conditions, and the dose and magnitude-dependent shifts were most evident on the DRL 29.5-s schedule. Experiment 2 compared the differences between acute and chronic dosing regimens (0.3 mg/kg nicotine) on DRL 29.5-s schedule responding. After 20 consecutive sessions of nicotine dosing, accuracy deteriorated significantly, demonstrating that chronic nicotine dosing leads to a behavioral sensitization apparent on the DRL 29.5-s schedule. The results from both experiments suggest that responding on the DRL 29.5-s schedule is sensitive to both dose–response and regimen-dependent effects of nicotine.

Assessing the Geographic Distribution of Centers for Independent Living Across Urban and Rural Areas Toward a Policy of Universal Access

Centers for Independent Living (CILs) have emerged as a significant source of services, supports, and advocacy for people with disabilities in the United States. Since 1978, the federal government has funded an increasing number of CILs around the nation to provide services to and advocate for people with disabilities. Others have been created with state and local funding. No data have been collected to assess the extent of CIL expansion, however. We identified 336 CILs and estimated that these centers operate 253 subordinate sites. We conducted a survey of a random sample of 62 CILs to assess the geographic areas they served and the extent of their service. Results suggested that CIL services are provided to more than 212,000 individuals living in 60% of the nations 3,141 counties. Data show, however, that residents of nonmetropolitan (rural) counties are far less likely to receive direct services from a CIL than their urban counterparts. CILs reported a median annual budget of

Increased effort requirements and risk sensitivity: a comparison of delay and magnitude manipulations

327,691; they allocated 54% of their resources to direct services and 27% to community advocacy. We estimate that an additional

Response disinhibition evoked by the administration of nicotine and nicotine-associated contextual cues

71.5 million will be needed to achieve universal access to CIL services. Results are discussed in terms of the rural population of people with disabilities as representing a traditionally underserved group, and the need to expand CIL services to provide more equitable access for currently unserved and underserved U.S. populations.

Nicotine enhancement and reinforcer devaluation: Interaction with opioid receptors

Reward magnitude and delay to reward were independently manipulated in two separate experiments examining risk-sensitive choice in rats. A dual-running wheel apparatus was used and the tangential force resistance required to displace both wheels was low (50g) for half of the subjects, and high (120g) for the remaining subjects. Concurrent FI30-s and FI60-s schedules delivered equivalent amounts of food reward per unit time (i.e. 5 and 10 pellets of food, respectively), and these conditions served as the baseline treatment for all subjects. Variability, either in reward magnitude or delay, was introduced on the long-delay (60s) schedule during the second phase. All subjects were returned to the baseline condition in the third phase, and variability was introduced on the short-delay (30s) interval schedule during phase four. The subjects were again returned to the baseline condition in the fifth and final phase, ultimately yielding a five-phase ABACA design. Original baseline performance was characterized by a slight short-delay interval preference, and this pattern of performance was recovered with each subsequent presentation of the baseline condition. Overall, the data obtained from the reward magnitude and delay-to-reward manipulations were indistinguishable; subjects experiencing low-response effort requirement behaved in a risk-indifferent manner and subjects experiencing high-response effort requirement preferred the variable schedule. Implications for the daily energy budget rule on risk-sensitive foraging are discussed in light of these findings.

17β-estradiol replacement in ovariectomized female rats slows set 1 dorsolateral striatial-dependent learning and enhances learning of set 2 in an extradimensional set-shifting paradigm.

Nicotine causes dose-dependent alterations in accuracy on the differential-reinforcement of low-rate responding (DRL) 29.5-s schedule in rats. The current investigation evaluated whether nicotine-associated contextual cues can produce nicotine-like perturbations in DRL-schedule performance in the absence of nicotine. Nicotine and saline administrations occurred just prior to DRL 29.5-s schedule responding for sucrose solution, and two different experimental contexts (differentiated by visual, olfactory, and tactile cues) were utilized. All subjects (N=16) experienced two consecutive sessions of DRL-schedule responding per day. The experimental group (n=8) was exposed to saline immediately prior to the first session and 0.3mg/kg nicotine before the second session, and the context was changed between sessions. This sequence of saline and then nicotine administration, paired with two reliable contexts, persisted for 12 consecutive days and successive nicotine administrations corresponded with increasingly poorer performance on the DRL 29.5-s schedule. No nicotine was administered for days 13-20 during context testing, and the nicotine-associated context produced response disinhibition on the DRL schedule. Two control groups were included in the design; subjects in one control group (n=4) received saline in each context to verify that the contexts themselves were not exerting control over operant responding. To assess how explicit and non-explicit pairings of nicotine and contextual cues influenced DRL behavior, subjects in a second control group (n=4) were given nicotine prior to the second session, but the contexts were not altered between sessions. The results from this experiment suggest that environmental stimuli associated with nicotine exposure can come to elicit nicotine-induced performance decrements on a DRL 29.5-s schedule.

Substitutes for tobacco smoking: a behavioral economic analysis of nicotine gum, denicotinized cigarettes, and nicotine-containing cigarettes

In rats, nicotine enhances responding maintained by non-pharmacological reinforcers, and discontinuation of nicotine devalues those same reinforcers. The goal of this study was to assess the interaction of nicotine and opioid receptors and to evaluate the degree to which nicotine enhancement and nicotine-induced devaluation are related to opioid activation. Nicotine (0.4mg/kg), or nicotine plus naloxone (0.3 or 3.0mg/kg), was delivered to rats prior to progressive ratio (PR) schedule sessions in which sucrose was used as a reinforcer. PR-schedule responding was assessed during ten daily sessions of drug delivery, and for three post-dosing days/sessions. Control groups for this investigation included a saline-only condition, and naloxone-only (0.3 or 3.0mg/kg) conditions. When administered in conjunction with nicotine, both naloxone doses attenuated nicotine enhancement of the sucrose reinforcer, and the combination of the larger dose of naloxone (3.0mg/kg) with nicotine produced significant impairments in sucrose reinforced responding. When administered alone, neither dose of naloxone (0.3 & 3.0mg/kg) significantly altered responding in comparison to saline. Furthermore, when dosing was discontinued after ten once-daily doses, all nicotine groups (nicotine-only and nicotine+naloxone combination) demonstrated significant decreases in sucrose reinforcement compared to the saline group. Although opioid antagonism attenuated reinforcement enhancement by nicotine, it did not prevent reinforcer devaluation upon discontinuation of nicotine dosing, and the higher dose of naloxone (3.0mg/kg) produced decrements upon discontinuation on its own in the absence of nicotine.