Chained Schedule Of Reinforcement Research Articles

Oral Cannabidiol does not alter Alcohol Seeking and Self‐Administration in Baboons

BackgroundThe cannabinoid cannabidiol (CBD) is currently under investigation as a pharmacotherapy for alcohol use disorder. The aim of the present study was to examine whether acute and chronic treatment with pure CBD would decrease alcohol seeking and consumption behaviors or alter drinking patterns in male baboons with extensive histories of daily alcohol intake (1 g/kg/day). MethodsSeven male baboons self-administered oral alcohol (4% w/v) in a validated chained schedule of reinforcement (CSR) procedure that modeled periods of anticipation, seeking, and consumption. In Experiment 1, CBD (5–40 mg/kg) or vehicle (peanut oil, USP) was administered orally 15- or 90-minutes prior to the start of the session. In Experiment 2, oral doses of CBD (10–40 mg/kg) or vehicle were administered for 5 consecutive days during ongoing alcohol access under the CSR. In addition, behavioral observations were conducted to assess potential drug side effects (e.g., sedation, motor incoordination) following chronic CBD treatment immediately after the session and 24-hours after drug administration. ResultsAcross both experiments, baboons self-administered an average of 1 g/kg/day of alcohol under baseline conditions. Administration of acute or chronic CBD (150–1200 mg total CBD dose/day) that encompassed the purported therapeutic dose range did not significantly reduce alcohol seeking, self-administration or intake (g/kg). Drinking patterns (i.e., number of drinks/bouts, bout duration, nor interdrink interval) also were not altered. There were no observable behavioral disruptions following CBD treatment. ConclusionsIn sum, the current data do not support use of pure CBD as an effective pharmacotherapy to reduce ongoing excessive drinking.

Evaluation of mifepristone effects on alcohol-seeking and self-administration in baboons.

Mifepristone, a type II glucocorticoid receptor antagonist, is under investigation as a potential pharmacotherapy for alcohol use disorder. This study examined effects of chronic administration of mifepristone on alcohol-seeking and self-administration in large nonhuman primates. Adult baboons (n = 5) self-administered alcohol 7 days/week under a chained schedule of reinforcement (CSR). The CSR comprised 3 components in which distinct cues were paired with different schedule requirements, with alcohol available for self-administration only in the final component, to model different phases of alcohol anticipation, seeking, and consumption. Under baseline conditions, baboons self-administered an average of 1g/kg/day of alcohol in the self-administration period. Mifepristone (10, 20, and 30 mg/kg) or vehicle was administered orally 30 min before each CSR session for 7 consecutive days. In a separate group of baboons (n = 5) acute doses of mifepristone (10, 20, and 30 mg/kg) were administered, and blood samples were collected over 72 hr to examine mifepristone pharmacokinetics. Some samples also were collected from the baboons that self-administered alcohol under the CSR after the chronic mifepristone condition. Mifepristone did not alter alcohol-seeking or self-administration under the CSR when compared with the vehicle condition. Mifepristone pharmacokinetics were nonlinear, and appear to be capacity limited. In sum, mifepristone did not reduce alcohol-maintained behaviors when administered to baboons drinking 1g/kg daily. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

The effects of varenicline on alcohol seeking and self-administration in baboons.

Nicotinic acetylcholine receptors (nAChRs) may play a critical role in alcohol reinforcement and consumption. The effects of varenicline, an nAChR partial agonist, on alcohol seeking and self-administration responses were evaluated in 2 groups of baboons trained under a 3-component chained schedule of reinforcement (CSR). Alcohol (4% w/v; n=4; alcohol group) or a preferred nonalcoholic beverage (n=4; control group) was available for self-administration only in component 3 of the CSR. Responses in component 2, required to gain access to alcohol, provided indices of seeking behavior. Varenicline (0.032 to 0.32mg/kg; 0.32mg/kg twice daily [BID]) and vehicle were administered before CSR sessions subchronically (5 consecutive days). Higher doses (0.56, 1.0mg/kg) were attempted, but discontinued due to adverse effects. Subchronic varenicline administration significantly (p<0.05) decreased the seeking response rate and increased the time to complete the response requirement to gain access to the daily supply of alcohol at the higher doses (0.32mg/kg, 0.32mg/kg BID dosing) in the alcohol group compared with the control group. Mean number of drinks was significantly decreased (p<0.05), but effects did not differ between groups. The pattern of drinking was characterized by a high rate during an initial bout. Number of drinks during and duration of the initial bout were significantly decreased in the alcohol group, compared with the control group, at 0.32mg/kg (p<0.05). Varenicline may be clinically useful for reducing alcohol-seeking behaviors prior to alcohol exposure. Given the modest effects on drinking itself, varenicline may be better suited as a treatment in combination with a pharmacotherapy that significantly reduces alcohol consumption.

Effects of the benzodiazepine GABAA α1-preferring ligand, 3-propoxy-β-carboline hydrochloride (3-PBC), on alcohol seeking and self-administration in baboons

The various α subtypes of GABAA receptors have been strongly implicated in alcohol reinforcement and consumption. The effects of the GABAA α1-preferring ligand, 3-propoxy-β-carboline hydrochloride (3-PBC), on seeking and self-administration responses were evaluated in two groups of baboons trained under a 3-component chained schedule of reinforcement (CSR). Alcohol (4% w/v; n = 5; alcohol group) or a preferred nonalcoholic beverage (n = 4; control group) was available for self-administration only in component 3 of the CSR. Responses in component 2 provided indices of motivation to drink (seeking). 3-PBC (1.0-30.0mg/kg) and saline were administered before drinking sessions under both acute and 5-day dosing conditions. Repeated, and not acute, doses of 3-PBC significantly decreased total self-administration responses (p < 0.05), volume consumed (p < 0.05), and gram per kilogram of alcohol (p < 0.05) in the alcohol group. In the control group, 5-day administration of 3-PBC significantly decreased total self-administration responses (p < 0.05) but produced nonsignificant decreases in volume consumed. Within-session pattern of drinking was characterized by a high level of drinking in the first 20min of the session for both groups, which was significantly (p < 0.05) decreased by all doses of 3-PBC (1.0-18.0mg/kg) only in the alcohol group. In contrast, the first drinking bout in the control group was only reduced at the highest doses of 3-PBC (10.0 and 18.0mg/kg). The results support the involvement of the GABAA α1 subtype receptor in alcohol reinforcement and consumption.

Baclofen effects on alcohol seeking, self-administration and extinction of seeking responses in a within-session design in baboons

Baclofen, a gamma-aminobutyric acidB receptor agonist, is currently under investigation as a potential treatment to prevent relapse to drinking in alcohol-dependent persons. In the current study, two groups of baboons were trained under a chained schedule of reinforcement (CSR), with three linked components, which were each correlated with different response requirements and cues. Fulfilling the requirement in the second link initiated the third link where either alcohol (n = 4) or a preferred non-alcoholic beverage (Tang, n = 5) was available for self-administration; failure to complete the response requirement in Link 2 ended the session (no access to alcohol or Tang). Seeking responses in Link 2 were used as indices of the motivational processes thought to be involved in relapse. The effects of baclofen (0.1-2.4 mg/kg) were examined under conditions with alcohol or Tang access and under extinction. Under the CSR, baclofen (1.8 and 2.4 mg/kg) significantly decreased (P < 0.05) alcohol self-administration responses and total g/kg alcohol intake. In contrast, only the highest dose of baclofen (2.4 mg/kg) reduced Tang self-administration and consumption. Under within-session extinction conditions, baclofen (1.8 and 2.4 mg/kg) facilitated extinction of responding for both alcohol and Tang, particularly during the first 10 minutes of extinction. Baclofen may be effective in reducing craving and alcohol drinking, although the facilitation of extinction and suppression of both alcohol and Tang self-administration by baclofen suggests these effects may be related to a more general suppression of consummatory and conditioned behaviors.

Effects of naltrexone on alcohol drinking patterns and extinction of alcohol seeking in baboons

Understanding naltrexone's effect on motivation to drink and pattern of drinking is important for better treatment outcomes and for comparison with novel medications. Naltrexone's effects on number and pattern of seeking, self-administration, and extinction responses were evaluated in two groups of baboons trained under a three-component chained schedule of reinforcement (CSR). Alcohol (4 % w/v; n = 4; alcohol group) or a preferred nonalcoholic beverage (n = 4; control group) was available for self-administration only in component 3 of the CSR. Responses in component 2 provided indices of motivation to drink (seeking). Naltrexone (0.32-3.2 mg/kg) and saline were administered before drinking and component 2 extinction sessions. Acute doses of naltrexone significantly decreased total self-administration responses (p < 0.01), intake volume (p < 0.001), and grams per kilogram of alcohol (p < 0.01) in the alcohol group only. Pattern of drinking did not change, but the number of drinks during the initial drinking bout was decreased significantly by naltrexone for both groups (p < 0.05). During within-session extinction tests, acute naltrexone significantly decreased time to reach extinction (p < 0.01) and number of seeking responses (p < 0.05), particularly early in the extinction period in the alcohol group only. When administered chronically, naltrexone did not decrease progressive ratio breaking points to gain access to alcohol, but dose dependently reduced alcohol self-administration (p < 0.05) by decreasing the magnitude of the initial drinking bout. The results support clinical observations that naltrexone may be most effective at reducing self-administration in the context of ongoing alcohol availability and may reduce motivation to drink in the presence of alcohol-related cues.

An account of human “impulsivity” on self-control tasks

Three experiments examined the effects of economic constraint (time restriction—trials restriction) on adult humans' performance on concurrent chained schedules of reinforcement in which terminal links differed both in reward size and pre-reward delay levels. In the first, terminal links offered a long delay (20, 30, 40, 50 sec) followed by 2 points, or a short delay (10 sec) followed by 1 point. Initial links consisted of the same variable interval schedules for each alternative. Subjects showed a conditional sensitivity to increases in delay. Under a time constraint, there was an increasing preference for the smaller reward as the delay to the larger reward was increased, whereas under a trials constraint subjects were totally insensitive to such changes. In the second experiment, this finding was replicated using long and short periods of video game playing as large and small rewards. In the third experiment terminal link parameters remained constant (2 points after 15 sec, or 1 point immediately), but...

CONTINGENCY AND STIMULUS CHANGE IN CHAINED SCHEDULES OF REINFORCEMENT

Higher rates of pecking were maintained by pigeons in the middle component of three-component chained fixed-interval schedules than in that component of corresponding multiple schedules (two extinction components followed by a fixed-interval component). This rate difference did not occur in equivalent tandem and mixed schedules, in which a single stimulus was correlated with the three components. The higher rates in components of chained schedules demonstrate a reinforcing effect of the stimulus correlated with the next component; the acquired functions of this stimulus make the vocabulary of conditioned reinforcement appropriate. Problems in defining conditioned reinforcement arise not from difficulties in demonstrating reinforcing effects but from disagreements about which experimental operations allow such reinforcing effects to be called conditioned.