Interactions among unit-price, fixed-ratio value, and dosing regimen in determining effects of repeated cocaine administration

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Under multiple schedules of reinforcement, previous research has generally observed tolerance to the rate-decreasing effects of cocaine that has been dependent on schedule-parameter size in the context of fixed-ratio (FR) schedules, but not under the context of fixed-interval (FI) schedules of reinforcement. The current experiment examined the effects of cocaine on key-pecking responses of White Carneau pigeons maintained under a three-component multiple conjunctive FI (10 s, 30 s, & 120 s) FR (5 responses) schedule of food presentation. Dose-effect curves representing the effects of presession cocaine on responding were assessed in the context of (1) acute administration of cocaine (2) chronic administration of cocaine and (3) daily administration of saline. Chronic administration of cocaine generally resulted in tolerance to the response-rate decreasing effects of cocaine, and that tolerance was generally independent of relative FI value, as measured by changes in ED50 values. Daily administration of saline decreased ED50 values to those observed when cocaine was administered acutely. The results show that adding a FR requirement to FI schedules is not sufficient to produce schedule-parameter-specific tolerance. Tolerance to cocaine was generally independent of FI-parameter under the present conjunctive schedules, indicating that a ratio requirement, per se, is not sufficient for tolerance to be dependent on FI parameter.

Section: Discussionsupporting

confidence: 83%

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confidence: 77%

Influences on Cocaine Tolerance Assessed Under a Multiple Conjunctive Schedule of Reinforcement

Yoon¹,

Branch²

2009

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“…With daily presession administration of a dose of cocaine that decreased response rates, tolerance to these behavioral effects developed under the FR 5 schedule, but did so less or not at all under the larger value FR schedules. This finding may be referred to as scheduleparameter-related tolerance, and has been obtained in a variety of species (Hughes & Branch, 1991;van Haaren & Anderson, 1994), with different drug types (Hughes et al, 2005;Nickel & Poling, 1990), and with different types and values of ratio schedules (Branch, 1990;Nickel et al, 1993;Yoon & Branch, 2004). These findings have led to subsequent studies attempting to clarify behavioral mechanism(s) involved in producing scheduleparameter-related tolerance.…”

Section: _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ __ _ _ _ _ _ _ _ _mentioning

confidence: 99%

“…For example, contingencies of reinforcement can influence drug tolerance (e.g., Branch, 1990;Hoffman, Branch, & Sizemore, 1987;Hughes & Branch, 1991;Hughes, Sigmon, Pitts, & Dykstra, 2005;Nickel, Alling, Kleiner, & Poling 1993;Pinkston & Branch, 2004;van Haaren & Anderson, 1994;Yoon & Branch, 2004). As an illustration, Hoffman et al (1987) studied the development of tolerance to effects of cocaine on behavior under a multiple fixed-ratio (FR) schedule with FR values of 5, 25, and 125 (FR 50 for one subject).…”

mentioning

confidence: 99%

Tolerance to Effects of Cocaine on Behavior Under a Response‐initiated Fixed‐interval Schedule

Weaver

Branch

2008

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Tolerance to effects of cocaine can be modulated by schedules of reinforcement. With multiple ratio schedules, research has shown an inverse relationship between ratio requirement and amount of tolerance that resulted from daily administration of the drug. In contrast, tolerance to the effects of cocaine on behavior under multiple interval schedules generally has developed regardless of interval value. Under interval schedules reinforcement depends on the animal making one response following a time interval. Thus, as time to respond increases, the time to reinforcement decreases. On the other hand, fixed ratio schedules require a specified number of responses to be made prior to reinforcement. Therefore, delaying the initiation of responding does not coincide with a significant decrease in the time to reinforcement. In the current experiment, 6 pigeons were trained to respond under a threecomponent multiple schedule, with a different tandem fixed-ratio 1 fixed-interval schedule in each component. The multiple schedule required one response, which was followed by one of three fixedinterval values (5, 15, or 60 s). Thus, the multiple schedule was interval-like because after the fixed-ratio 1, only one more response was required for reinforcement, but it was also ratio-like because the length of the pause at the beginning of each interreinforcer interval affected the time until the next reinforcer. Acute administration of cocaine generally resulted in dose-dependent decreases in responding. Chronic (i.e., daily) administration of a rate-decreasing dose resulted in tolerance patterns similar to those usually obtained with multiple ratio schedules. That is, the magnitude of tolerance was related inversely to schedule size. These results suggest that delay to reinforcement from the initial response may play a role in the development of schedule-parameter-related tolerance.Key words: cocaine, tolerance, fixed-interval schedules, fixed-ratio schedules, tandem schedules, key peck, pigeonsDrug tolerance is characterized by three features: (1) it often occurs after repeated or prolonged exposure, (2) it is revealed as a loss of effect relative to the drug's initial impact, and (3) in most cases, more of the substance is required to attain the initial effect (Carlton, 1983;Rang, Dale, Ritter, & Moore, 2003). Tolerance can be illustrated as a shift to the right of the dose-response function, and has been implicated as a contributing factor to drug abuse and is also of concern for clinical therapeutics (O'Brien, 2001).Previous research has illustrated that environmental circumstances may play a significant role in the development of tolerance (for reviews see Branch, 1991;Carlton, 1983;Stewart & Badiani, 1993;Wolgin, 1989). For example, contingencies of reinforcement can influence drug tolerance (e.g., Branch, 1990;Hoffman, Branch, & Sizemore, 1987;Hughes & Branch, 1991;Hughes, Sigmon, Pitts, & Dykstra, 2005;Nickel, Alling, Kleiner, & Poling 1993;Pinkston & Branch, 2004;van Haaren & Anderson, 1994;Yoon & Branch, 2004). As an ...

“…That is, tolerance generally is more substantial for responding under small-ratio components, and not under large-ratio components, of a multiple schedule (Branch, 1990; Hoffman et al, 1987; Hughes & Branch, 1991; Nickel & Poling, 1990; Nickel et al, 1993; Pinkston & Branch, 2004; Van Haaren & Anderson, 1994; Yoon & Branch, 2004). A noteworthy feature of the present data was that for four of five pigeons, some degree of tolerance developed in the large-ratio component.…”

Section: Discussionmentioning

confidence: 99%

Tolerance to cocaine's effects following chronic administration of a dose without detected effects on response rate or pause

Minervini

Branch

2013

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To observe tolerance to drug effects on operant behavior, the dose that researchers have often selected for chronic administration is one that disrupts, but does not abolish, responding. Some evidence suggests that tolerance may develop after chronic administration of relatively smaller doses. The purpose of the present experiment was to assess systematically effects of chronic administration of a dose without detected effect on responding. Specifically, response rates and postreinforcement pauses of five pigeons key pecking under a three-component multiple fixed-ratio schedule of food reinforcement were observed under chronic cocaine administration. We evaluated the effects of a range of doses (1.0 mg/kg to 17.0 mg/kg) during acute administration. The largest dose that failed to alter responding acutely then was administered chronically (1.0 mg/kg for one pigeon, 3.0 mg/kg for three pigeons, and 5.6 mg/kg for one pigeon). After 30 consecutive sessions of chronic administration, smaller and larger doses occasionally were substituted for the chronic dose. Pigeons then received presession saline administration for 30 consecutive sessions, and the postchronic effects of the series of doses on responding were determined. All subjects developed tolerance to doses of cocaine that initially had caused large decreases in rate, with the magnitude of the effects varying across components of the multiple schedule and subjects. Specifically, tolerance generally was greatest in the components with smaller ratios. Following postchronic saline administration, tolerance was usually diminished. Overall, the results demonstrate that under these conditions, repeated experience with disruptive effects of cocaine on food-maintained responding is not a necessary factor in the development of tolerance.