Tolerance to effects of cocaine on schedule-controlled behavior: Effects of fixed-interval schedule parameter

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Four squirrel monkeys responded daily under a fixed-interval 5-min or 8-min schedule of food-pellet delivery. Cocaine (0.03 to 1.7 mg/kg) and saline were injected before occasional daily sessions (acute administration). Some doses of cocaine produced substantial overall increases in response rate for 3 of the subjects; effects were less substantial for the remaining subject, who exhibited modest increases in response rate early in the session and during the middle portion of the intervals. A dose that increased response rate when administered acutely was then administered before each session (chronic administration). Chronic administration resulted in a reduction in the increases in response rate seen under acute administration for all subjects.Key words: fixed-interval schedules, cocaine, behavioral tolerance, lever press, squirrel monkeyBehavioral effects of repeated cocaine exposure depend on many factors. An early report by Tatum and Seevers (1929) that after repeated exposure, behavior can become more sensitive to the drug has been confirmed by others (Post & Rose, 1976; Woolverton, Kandel, & Schuster, 1978b). In contrast to studies reporting sensitization, other research shows that behavior can become less sensitive to cocaine (tolerance) after repeated administration (e.g., Branch & Sizemore, 1988;Moore & Thompson, 1978;Woolverton et al., 1978b;Woolverton, Kandel, & Schuster, 1978a fects of 1.0 mg/kg d-amphetamine when reinforcement rate was initially disrupted during a schedule that reinforced interresponse times greater than 30 s (Schuster, Dockens, & Woods, 1966). However, tolerance to rate-increasing effects did not occur when reinforcement rate was not disrupted under a fixed-interval (FI) 30-s schedule. Thus, the effects of repeated administration of d-amphetamine depended on its initial effects on reinforcement rate. This has become known as the reinforcement-loss hypothesis, and has been applied to drugs other than amphetamines, including cocaine (Moore & Thompson, 1978;Woolverton et al., 1978aWoolverton et al., , 1978b.Although interactions between the behavioral effects of drugs and the consequences of behavior have been shown to be important (Smith & McKearney, 1977;van Haaren, 1992), the lack of tolerance to stimulant-induced rate increases on FT performance reported by Schuster et al. (1966) is not a consistent finding. One additional study found little change in cocaine's rate-increasing effects on FI shock-termination responding of squirrel monkeys when the drug was infused continuously (0.1 and 0.3 mg/kg/hr) for 2 weeks (Howell & Morse, 1989). However, reduction in initial rate increases has been reported after studying 0.16 mg/kg d-amphetamine and 0.5 mg/kg 1-amphetamine on FI food-maintained responding of rats (Tilson & Sparber, 1973), and after studying effects of 0.1 mg/kg d-amphetamine on FI responding of squirrel monkeys maintained by food delivery, shock termination, or shock delivery (Branch, 1979) when drugs were administered once daily before sessions. Thus, studies that have pr...

Section: Resultssupporting

confidence: 76%

Tolerance to Cocaine's Rate‐increasing Effects Upon Repeated Administration

Schama

Branch

1994

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“…For example, although parameter-dependent rate suppression has frequently been observed under ratio schedules, the effects obtained with comparable interval schedules are often not parameter dependent (Branch, 1990;Schama & Branch, 1989). Cohen's (1986) tests of d-amphetamine in rats lever pressing on chained and multiple Fl or random-interval schedules produced little evidence of schedule or link dependence, and hence also fail to support the responsestrength interpretation.…”

Section: Discussionmentioning

confidence: 99%

Cocaine's Effects on Food‐reinforced Pecking in Pigeons Depend on Food‐deprivation Level

Schaal

Miller

Odum

1995

Four pigeons deprived to 80% of their laboratory free-feeding weights pecked keys under a multiple fixed-ratio 30 fixed-interval 5-min schedule of food presentation. Components alternated strictly with 15-s timeouts separating them; each was presented six times. When rates of pecking were stable, 2 pigeons' weights were reduced to 70%, and the other 2 pigeons' weights were increased to 82.5% to 85% of free-feeding levels. Cocaine (1.0, 3.0, 5.6, and 10.0 mg/kg and saline) was administered 5 min prior to sessions. When each dose had been tested twice, pigeons' weights were adjusted to the level that they had not yet experienced, and cocaine was tested again. Cocaine reduced response rates in a dose-dependent manner under the fixed-ratio schedule and under the fixed-interval schedule at high doses, and increased rates under the fixed-interval schedule at low doses. Reductions in pecking rates occurred at lower doses under both schedules in 3 of 4 pigeons when they were less food deprived compared to when they were more food deprived. Low doses of cocaine increased low baseline rates of pecking in the initial portions of the fixed-interval schedules by a greater magnitude when pigeons were more food deprived. Thus, food-deprivation levels altered both the rate-decreasing and rate-increasing effects of cocaine. The implications of these results for the mechanisms by which food deprivation increases cocaine self-administration and for the dependence of cocaine's effects on the baseline strength of operant behavior are discussed.Key words: cocaine, fixed-interval schedules, fixed-ratio schedules, food deprivation, key peck, pigeon Changes in levels of food deprivation of nonhuman subjects have been shown to alter several behavioral effects of drugs profoundly. Studies have shown that the rate-suppressive effects of drugs on operant behavior are obtained at lower doses when animals are less food deprived than when they are more severely food deprived (Cole, 1967;Gollub & Mann, 1969;Kelly & Thompson, 1988;Samson, 1986;Schaal & Branch, 1992

“…The final schedule was a three-component multiple RIFI schedule, with parameter values in the different components of 5, 15, and 60 s. The values were chosen because they are roughly 50% of the FI values employed by Schama and Branch (1989). Prior research suggests that the average PRP for fixed-interval schedules is roughly 50% of the interreinforcement interval (Powell, 1968;Schneider, 1969;Shull, 1971;Zeiler & Powell, 1994).…”

Section: Behavioral Proceduresmentioning

confidence: 99%

“…Schama and Branch (1989) directly examined the role of reinforcement rate by exposing pigeons to a three-component multiple fixed-interval (FI) schedule, in which the FI values (FI 5, 20, and 120 s) approximated baseline rates of reinforcement obtained in the Hoffman et al (1987) study. In contrast to the previous study with FR schedules, roughly equivalent amounts of tolerance developed for all three FI schedule parameters.…”

Section: _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ __ _ _ _ _ _ _ _ _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 ...